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1.
Cureus ; 16(7): e64807, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39156412

RESUMEN

Craniosacral treatment (CST) is an osteopathic technique grounded in the assumption that there is an intrinsic, fine movement of the cerebrospinal fluid. This rhythmic movement can be utilized for diagnostic and therapeutic purposes by palpation and manipulation of the skull, spine, and associated connective tissues. Therapeutic benefit is likely due to action on the autonomic nervous system (ANS), specifically through the vagus nerve. Current literature on the neurophysiological effects of CST is limited, which has contributed to controversy regarding its effectiveness. Heart rate variability (HRV) as a measure of cardiovascular stress and autonomic system activity is thus proposed as a tool to evaluate the neurophysiologic effects of CST. HRV can be analyzed in two different bands, high-frequency (HF) and low-frequency (LF) power associated with a parasympathetic and sympathetic response. In this meta-analysis, we provide a brief introduction to CST, analyze three primary studies, and summarize the therapeutic benefits and pitfalls of this alternative treatment on the ANS. A significant negative HF standardized mean difference after CST was observed; standardized mean difference = -0.46; 95% CI (-0.79,-0.14). No significant effect on LF power was observed. We conclude that CST does provide a moderate short-term increase in parasympathetic activity. These findings suggest that CST may be used to treat patients with an overactive sympathetic state. Further studies should be conducted for comparison against a control group to eliminate the possibility of a placebo effect and to elucidate long-term effects.

2.
3D Print Med ; 10(1): 26, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102099

RESUMEN

BACKGROUND: . Mitral transcatheter edge-to-edge repair (m-TEER) is a minimally invasive procedure for treating mitral regurgitation (MR). m-TEER is a highly technical procedure, and a steep learning curve needs to be overcome for operators to ensure optimal patient outcomes and minimise procedural complications. Training via online simulation and observation of procedures is not sufficient to establish operator confidence; thus, advanced hands-on training modalities need to be explored and developed. METHODS: . In this study, a novel anatomical simulator for m-TEER training was evaluated in comparison to a standard model. The proposed simulator resembled the anatomical features of the right and left atrium, left ventricle and mitral valve apparatus. Participants in the questionnaire (n = 18) were recruited across 4 centres in London with (n = 8) and without (n = 10) prior experience in m-TEER. Participants were asked to simulate procedures on both an idealised, routinely used simulator and the newly proposed anatomical model. The questionnaire was designed to assess (i) participants' confidence before and after training and (ii) the realism of the model in the context of the m-TEER procedure. The results of the questionnaires were collected, and statistical analysis (t-test) was performed. RESULTS: . Both models were equally beneficial in increasing operator confidence before and after the simulation of the intervention (P = 0.43). However, increased confidence after training with the anatomical model was recorded (P = 0.02). Participants with prior experience with m-TEER therapy were significantly more confident about the procedure after training with the anatomical model than participants who had no prior experience (P = 0.002). On average, all participants thought that the anatomical model was effective as a training simulator (P = 0.013) and should be integrated into routine training (P = 0.015)). Participants with experience thought that the anatomical model was more effective at reproducing the m-TEER procedure than the idealised model (P = 0.03). CONCLUSIONS: . This study showed how a more realistic simulator can be used to improve the effectiveness of m-TEER procedural training. Such pilot results suggest planning future and large investigations to evaluate improvements in clinical practice.

3.
Radiology ; 312(1): e232731, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-39012246

RESUMEN

Background Current clinical imaging modalities such as CT and MRI provide resolution adequate to diagnose cardiovascular diseases but cannot depict detailed structural features in the heart across length scales. Hierarchical phase-contrast tomography (HiP-CT) uses fourth-generation synchrotron sources with improved x-ray brilliance and high energies to provide micron-resolution imaging of intact adult organs with unprecedented detail. Purpose To evaluate the capability of HiP-CT to depict the macro- to microanatomy of structurally normal and abnormal adult human hearts ex vivo. Materials and Methods Between February 2021 and September 2023, two adult human donor hearts were obtained, fixed in formalin, and prepared using a mixture of crushed agar in a 70% ethanol solution. One heart was from a 63-year-old White male without known cardiac disease, and the other was from an 87-year-old White female with a history of multiple known cardiovascular pathologies including ischemic heart disease, hypertension, and atrial fibrillation. Nondestructive ex vivo imaging of these hearts without exogenous contrast agent was performed using HiP-CT at the European Synchrotron Radiation Facility. Results HiP-CT demonstrated the capacity for high-spatial-resolution, multiscale cardiac imaging ex vivo, revealing histologic-level detail of the myocardium, valves, coronary arteries, and cardiac conduction system across length scales. Virtual sectioning of the cardiac conduction system provided information on fatty infiltration, vascular supply, and pathways between the cardiac nodes and adjacent structures. HiP-CT achieved resolutions ranging from gross (isotropic voxels of approximately 20 µm) to microscopic (approximately 6.4-µm voxel size) to cellular (approximately 2.3-µm voxel size) in scale. The potential for quantitative assessment of features in health and disease was demonstrated. Conclusion HiP-CT provided high-spatial-resolution, three-dimensional images of structurally normal and diseased ex vivo adult human hearts. Whole-heart image volumes were obtained with isotropic voxels of approximately 20 µm, and local regions of interest were obtained with resolution down to 2.3-6.4 µm without the need for sectioning, destructive techniques, or exogenous contrast agents. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Bluemke and Pourmorteza in this issue.


Asunto(s)
Corazón , Tomografía Computarizada por Rayos X , Humanos , Persona de Mediana Edad , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Corazón/diagnóstico por imagen , Anciano de 80 o más Años , Cardiopatías/diagnóstico por imagen , Sincrotrones
4.
Trials ; 25(1): 473, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992786

RESUMEN

INTRODUCTION: n-of-1 trials are undertaken to optimise the evaluation of health technologies in individual patients. They involve a single patient receiving treatments, both interventional and control, consecutively over set periods of time, the order of which is decided at random. Although n-of-1 trials are undertaken in medical research it could be argued they have the utility to be undertaken more frequently. We undertook the National Institute for Health Research (NIHR) commissioned DIAMOND (Development of generalisable methodology for n-of-1 trials delivery for very low volume treatments) project to develop key points to assist clinicians and researchers in designing and conducting n-of-1 trials. METHODS: The key points were developed by undertaking a stakeholder workshop, followed by a discussion within the study team and then a stakeholder dissemination and feedback event. The stakeholder workshop sought to gain the perspectives of a variety of stakeholders (including clinicians, researchers and patient representatives) on the design and use of n-of-1 trials. A discussion between the study team was held to reflect on the workshop and draft the key points. Lastly, the stakeholders from the workshop were invited to a dissemination and feedback session where the proposed key points were presented and their feedback gained. RESULTS: A set of 22 key points were developed based on the insights from the workshop and subsequent discussions. They provide guidance on when an n-of-1 trial might be a viable or appropriate study design and discuss key decisions involved in the design of n-of-1 trials, including determining an appropriate number of treatment periods and cycles, the choice of comparator, recommended approaches to randomisation and blinding, the use of washout periods and approaches to analysis. CONCLUSIONS: The key points developed in the project will support clinical researchers to understand key considerations when designing n-of-1 trials. It is hoped they will support the wider implementation of the study design.


Asunto(s)
Proyectos de Investigación , Investigadores , Participación de los Interesados , Humanos , Consenso , Ensayos Clínicos como Asunto/métodos , Evaluación de la Tecnología Biomédica , Resultado del Tratamiento
5.
Nature ; 631(8020): 360-368, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926570

RESUMEN

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophila melanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographic nanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.


Asunto(s)
Conectoma , Drosophila melanogaster , Neuronas Motoras , Tejido Nervioso , Vías Nerviosas , Sinapsis , Animales , Femenino , Conjuntos de Datos como Asunto , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Drosophila melanogaster/ultraestructura , Extremidades/fisiología , Extremidades/inervación , Holografía , Microscopía Electrónica , Neuronas Motoras/citología , Neuronas Motoras/fisiología , Neuronas Motoras/ultraestructura , Movimiento , Músculos/inervación , Músculos/fisiología , Tejido Nervioso/anatomía & histología , Tejido Nervioso/citología , Tejido Nervioso/fisiología , Tejido Nervioso/ultraestructura , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Vías Nerviosas/ultraestructura , Sinapsis/fisiología , Sinapsis/ultraestructura , Tomografía por Rayos X , Alas de Animales/inervación , Alas de Animales/fisiología
6.
Nature ; 631(8020): 369-377, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38926579

RESUMEN

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles1. MN activity is coordinated by complex premotor networks that facilitate the contribution of individual muscles to many different behaviours2-6. Here we use connectomics7 to analyse the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. By contrast, wing premotor networks lack proportional synaptic connectivity, which may enable more flexible recruitment of wing steering muscles. Through comparison of the architecture of distinct motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.


Asunto(s)
Conectoma , Drosophila melanogaster , Extremidades , Neuronas Motoras , Vías Nerviosas , Sinapsis , Alas de Animales , Animales , Femenino , Masculino , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Extremidades/inervación , Extremidades/fisiología , Neuronas Motoras/fisiología , Movimiento/fisiología , Músculos/inervación , Músculos/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/citología , Red Nerviosa/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Sinapsis/fisiología , Alas de Animales/inervación , Alas de Animales/fisiología
7.
Dalton Trans ; 53(22): 9262-9266, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38776119

RESUMEN

First-of-a-kind temperature-controlled electron pulse radiolysis experiments facilitated the radiation-induced formation of Am(IV) in concentrated (6.0 M) HNO3, and enabled the derivation of Arrhenius and Eyring activation parameters for instigating the radical reaction between NO3˙ and Am(III).

8.
bioRxiv ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38712128

RESUMEN

Somatosensory neurons provide the nervous system with information about mechanical forces originating inside and outside the body. Here, we use connectomics to reconstruct and analyze neural circuits downstream of the largest somatosensory organ in the Drosophila leg, the femoral chordotonal organ (FeCO). The FeCO has been proposed to support both proprioceptive sensing of the fly's femur-tibia joint and exteroceptive sensing of substrate vibrations, but it remains unknown which sensory neurons and central circuits contribute to each of these functions. We found that different subtypes of FeCO sensory neurons feed into distinct proprioceptive and exteroceptive pathways. Position- and movement-encoding FeCO neurons connect to local leg motor control circuits in the ventral nerve cord (VNC), indicating a proprioceptive function. In contrast, signals from the vibration-encoding FeCO neurons are integrated across legs and transmitted to auditory regions in the brain, indicating an exteroceptive function. Overall, our analyses reveal the structure of specialized circuits for processing proprioceptive and exteroceptive signals from the fly leg. They also demonstrate how analyzing patterns of synaptic connectivity can distill organizing principles from complex sensorimotor circuits.

9.
Cureus ; 16(3): e56086, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38618351

RESUMEN

We present the case report of a patient with seronegative myasthenia gravis (MG) who was admitted for metabolic encephalopathy and acute on chronic hypoxic respiratory failure secondary to an MG crisis three days after an intravenous immunoglobulin treatment. In the intensive care unit, her MG was managed with intravenous immunoglobulin, plasmapheresis, prednisone, and pyridostigmine. During the course of her visit, she had urosepsis along with a left chest port that had cultured positive for Pseudomonas aeruginosa and developed a right upper extremity deep vein thrombosis (UEDVT) and superficial thrombosis in the left upper extremity despite being on heparin therapy. She had a transient drop in platelets to below 150,000 that resolved within a day. We analyzed the variables of this case report and reviewed the literature of similar cases to elucidate the factors that may have led to the development of the UEDVTs. The patient had many factors in her past medical history that could have contributed to her thrombosis including morbid obesity and prior history of pulmonary embolisms. It is hypothesized that MG disturbs the endothelial cell lining through an increased inflammatory state that could also be a causative factor. There is no definitive way we could link MG as a causative factor due to a lack of testing to assess alteration in the integrity or functionality of her endothelium. A case report we reviewed showed a presentation of UEDVT in an MG patient due to a thymoma compressing the subclavian vein. However, this is not the case in this example due to the patient having a history of thymectomy. She was also at risk due to her hospital stay which led to immobility and placement of a central venous catheter. We conclude the formation of the UEDVT was likely a combination of these factors.

10.
Trials ; 25(1): 263, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622638

RESUMEN

BACKGROUND: n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions. METHODS: Databases and clinical trials registries were searched for articles including "n-of-1" in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables. RESULTS: We identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo controlled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient-reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions. CONCLUSIONS: n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies. TRIAL REGISTRATION: Not applicable.

11.
J Anat ; 245(2): 201-216, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38629319

RESUMEN

Despite centuries of investigation, certain aspects of left ventricular anatomy remain either controversial or uncertain. We make no claims to have resolved these issues, but our review, based on our current knowledge of development, hopefully identifies the issues requiring further investigation. When first formed, the left ventricle had only inlet and apical components. With the expansion of the atrioventricular canal, the developing ventricle cedes part of its inlet to the right ventricle whilst retaining the larger parts of the cushions dividing the atrioventricular canal. Further remodelling of the interventricular communication provides the ventricle with its outlet, with the aortic root being transferred to the left ventricle along with the newly formed myocardium supporting its leaflets. The definitive ventricle possesses inlet, apical and outlet parts. The inlet component is guarded by the mitral valve, with its leaflets, in the normal heart, supported by papillary muscles located infero-septally and supero-laterally. There is but a solitary zone of apposition between the leaflets, which we suggest are best described as being aortic and mural. The trabeculated component extends beyond the inlet to the apex and is confluent with the outlet part, which supports the aortic root. The leaflets of the aortic valve are supported in semilunar fashion within the root, with the ventricular cavity extending to the sinutubular junction. The myocardial-arterial junction, however, stops well short of the sinutubular junction, with myocardium found only at the bases of the sinuses, giving rise to the coronary arteries. We argue that the relationships between the various components should now be described using attitudinally appropriate terms rather than describing them as if the heart is removed from the body and positioned on its apex.


Asunto(s)
Ventrículos Cardíacos , Humanos , Ventrículos Cardíacos/anatomía & histología , Animales
12.
Heliyon ; 10(4): e26629, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38434088

RESUMEN

Inversion of the left atrial appendage is a rare phenomenon, which may occur during the de-airing maneuvers associated to routinely performed surgery procedures, such as cardiopulmonary bypass or left ventricular assist device implantation. In this case, the body of the inverted appendage can obstruct the mitral valve leading to severe complications. The mechanisms are still poorly known, and more specific studies are needed to better understand its causes and identify mitigating strategies. The current study attempts to gain a better comprehension of the conditions and the factors favourable to left atrial appendage inversion. Four patient specific appendage morphologies, obtained from computerised tomography and representative of the main typologies commonly used for the appendage classification (chicken wing, cactus, cauliflower, and windsock), were used for the study. The numerical models were subjected to the same loading pattern, made of subsequent different pressure curves. Results show that the morphologies invert and recover their original anatomical configuration at different pressure loads, indicating that their tendency to invert is associated to their specific morphological features. Moreover, the analysis highlights that, although restoring the physiological left atrium pressure is not sufficient to induce appendage recovery, pressures well below the ventricular ones can induce the return to the natural configuration. All models recovered the anatomical configuration at pressures well below the ventricular pressure (about 100 mmHg), suggesting that basic trans-catheter maneuvers, e.g. producing temporary mitral regurgitation, could be attempted to correct the appendage configuration, prior to opt for more invasive surgical approaches.

13.
J Invertebr Pathol ; 204: 108084, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38452853

RESUMEN

Opportunistic bacterial infections are common in insect populations but there is little information on how they are acquired or transmitted. We tested the hypothesis that Macrocheles mites can transmit systemic bacterial infections between Drosophila hosts. We found that 24% of mites acquired detectable levels of bacteria after feeding on infected flies and 87% of infected mites passed bacteria to naïve recipient flies. The probability that a mite could pass Serratia from an infected donor fly to a naïve recipient fly was 27.1%. These data demonstrate that Macrocheles mites are capable of serving as vectors of bacterial infection between insects.


Asunto(s)
Ácaros , Animales , Ácaros/microbiología , Ácaros/fisiología , Drosophila/microbiología , Drosophila/parasitología , Serratia/fisiología , Drosophila melanogaster/microbiología
14.
Eur J Vasc Endovasc Surg ; 67(4): 540-553, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428672

RESUMEN

OBJECTIVE: Treatment of juxtarenal and complex neck abdominal aortic aneurysms (AAAs) is now commonly by endovascular rather than open surgical repair (OSR). Published comparisons show poor validity and scientific precision. UK-COMPASS is a comparative cohort study of endovascular treatments vs. OSR for patients with an AAA unsuitable for standard on label endovascular aneurysm repair (EVAR). METHODS: All procedures for AAA in England (November 2017 to October 2019) were identified, AAA anatomy assessed in a Corelab, peri-operative risk scores determined, and propensity scoring used to identify patients suitable for either endovascular treatment or OSR. Patients were stratified by aneurysm neck length (0 - 4 mm, 5 - 9 mm, or ≥ 10 mm) and operative risk; the highest quartile was considered high risk and the remainder standard risk. Death was the primary outcome measure. Endovascular treatments included fenestrated EVAR (FEVAR) and off label standard EVAR (± adjuncts). RESULTS: Among 8 994 patients, 2 757 had AAAs that were juxtarenal, short neck, or complex neck in morphology. Propensity score stratification and adjustment method comparisons included 1 916 patients. Widespread off label use of standard EVAR devices was noted (35.6% of patients). The adjusted peri-operative mortality rate was 2.9%, lower for EVAR (1.2%; p = .001) and FEVAR (2.2%; p = .001) than OSR (4.5%). In standard risk patients with a 0 - 4 mm neck, the mortality rate was 7.4% following OSR and 2.3% following FEVAR. Differences were smaller for patients with a neck length ≥ 5 mm: 2.1% OSR vs. 1.0% FEVAR. At 3.5 years of follow up, the overall mortality rate was 20.7% in the whole study population, higher following FEVAR (27.6%) and EVAR (25.2%) than after OSR (14.2%). However, in the 0 - 4 mm neck subgroup, overall survival remained equivalent. The aneurysm related mortality rate was equivalent between treatments, but re-intervention was more common after EVAR and FEVAR than OSR. CONCLUSION: FEVAR proves notably safer than OSR in the peri-operative period for juxtarenal aneurysms (0 - 4 mm neck length), with comparable midterm survival. For patients with short neck (5 - 9 mm) and complex neck (≥ 10 mm) AAAs, overall survival was worse in endovascularly treated patients compared with OSR despite relative peri-operative safety. This warrants further research and a re-appraisal of the current clinical application of endovascular strategies, particularly in patients with poor general survival outlook owing to comorbidity and age.

15.
Dalton Trans ; 53(16): 6881-6891, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38407412

RESUMEN

A systematic study of the impact on the chemical reactivity of the oxidising n-dodecane radical cation (RH˙+) with f-element complexed 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (HEH[EHP]) has been undertaken utilizing time-resolved electron pulse radiolysis/transient absorption spectroscopy and high-level quantum mechanical calculations. Lanthanide ion complexed species, [Ln((HEH[EHP])2)3], exhibited vastly increased reactivity (over 10× faster) in comparison to the non-complexed ligand in n-dodecane solvent, whose rate coefficient was k = (4.66 ± 0.22) × 109 M-1 s-1. Similar reactivity enhancement was also observed for the corresponding americium ion complex, k = (5.58 ± 0.30) × 1010 M-1 s-1. The vastly increased reactivity of these f-element complexes was not due to simple increased diffusion-control of these reactions; rather, enhanced hole transfer mechanisms for the complexes were calculated to become energetically more favourable. Interestingly, the observed reactivity trend with lanthanide ion size was not linear; instead, the rate coefficients showed an initial increase (Lu to Yb) followed by a decrease (Tm to Ho), followed by another increase (Dy to La). This behaviour was excellently predicted by the calculated reaction volumes of these complexes. Complementary cobalt-60 gamma irradiations for select lanthanide complexes demonstrated that the measured kinetic differences translated to increased ligand degradation at steady-state timescales, affording ∼38% increase in ligand loss of a 1 : 1 [La((HEH[EHP])2)3] : HEH[EHP] ratio system.

16.
Comput Methods Programs Biomed ; 246: 108056, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38330768

RESUMEN

BACKGROUND: Complications of atrial fibrillation (AF) include ischemic events originating within the left atrial appendage (LAA), a protrusion of the left atrium with variable morphological characteristics. The role of the patient specific morphology and pathological haemodynamics on the risk of ischemia remains unclear. METHODS: This work performs a comparative assessment of the hemodynamic parameters among patient-specific LAA morphologies through fluid-structure interaction computational analyses. Three LAA models per each of the four commons patient-specific morphological families (chicken wing, cactus, windsock, and cauliflower) were analysed. Mechanical properties of the tissue were based on experimental uniaxial tests on a young pig's heart. Boundary conditions were imposed based on clinical assessments of filling and emptying volumes. Sinus rhythm and atrial fibrillation operative conditions were simulated and analysed. RESULTS: For each model, the effect of morphological and functional parameters, such as the number of trabeculae and LAA stroke volume, over the hemodynamics established into the appendage was analysed. Comparison between results obtained in healthy and diseased conditions suggested the introduction of a new parameter to quantify the risk of thrombosis, here called blood stasis factor (BSF). This is defined as the LAA surface area which permanently experiences levels of shear strain rate inferior to a threshold value, set to 5 s-1 (BSF5). CONCLUSIONS: This work suggests that the current morphological classification is unsuitable to evaluate the probability of thrombus formation. However, hemodynamic parameters easy to determine from clinical examinations, such as normalised stroke volume, LAA orifice flow rate and presence of extensive trabeculations can identify departures from healthy hemodynamics in AF and support a more systematic stratification of the thromboembolic risk.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Humanos , Apéndice Atrial/patología , Hemodinámica
18.
Curr Biol ; 34(5): 1059-1075.e5, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38402616

RESUMEN

Natural behaviors are a coordinated symphony of motor acts that drive reafferent (self-induced) sensory activation. Individual sensors cannot disambiguate exafferent (externally induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to carry out adaptive behaviors through corollary discharge circuits (CDCs), which provide predictive motor signals from motor pathways to sensory processing and other motor pathways. Yet, how CDCs comprehensively integrate into the nervous system remains unexplored. Here, we use connectomics, neuroanatomical, physiological, and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs) in Drosophila, which function as a predictive CDC in other insects. Both AHN pairs receive input primarily from a partially overlapping population of descending neurons, especially from DNg02, which controls wing motor output. Using Ca2+ imaging and behavioral recordings, we show that AHN activation is correlated to flight behavior and precedes wing motion. Optogenetic activation of DNg02 is sufficient to activate AHNs, indicating that AHNs are activated by descending commands in advance of behavior and not as a consequence of sensory input. Downstream, each AHN pair targets predominantly non-overlapping networks, including those that process visual, auditory, and mechanosensory information, as well as networks controlling wing, haltere, and leg sensorimotor control. These results support the conclusion that the AHNs provide a predictive motor signal about wing motor state to mostly non-overlapping sensory and motor networks. Future work will determine how AHN signaling is driven by other descending neurons and interpreted by AHN downstream targets to maintain adaptive sensorimotor performance.


Asunto(s)
Drosophila , Neuronas , Animales , Drosophila/fisiología , Vías Eferentes , Insectos
19.
J Phys Chem A ; 128(3): 590-598, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38215218

RESUMEN

Despite the availability of transuranic elements increasing in recent years, our understanding of their most basic and inherent radiation chemistry is limited and yet essential for the accurate interpretation of their physical and chemical properties. Here, we explore the transient interactions between trivalent californium ions (Cf3+) and select inorganic radicals arising from the radiolytic decomposition of common anions and functional group constituents, specifically the dichlorine (Cl2•-) and sulfate (SO4•-) radical anions. Chemical kinetics, as measured using integrated electron pulse radiolysis and transient absorption spectroscopy techniques, are presented for the reactions of these two oxidizing radicals with Cf3+ ions. The derived and ionic strength-corrected second-order rate coefficients (k) for these radiation-induced processes are k(Cf3+ + Cl2•-) = (8.28 ± 0.61) × 105 M-1 s-1 and k(Cf3+ + SO4•-) = (9.50 ± 0.43) × 108 M-1 s-1 under ambient temperature conditions (22 ± 1 °C).

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