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1.
PLoS One ; 19(4): e0302021, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38625839

RESUMEN

Falls among older adults are a costly public health concern. Such falls can be precipitated by balance disturbances, after which a recovery strategy requiring rapid, high force outputs is necessary. Sarcopenia among older adults likely diminishes their ability to produce the forces necessary to arrest gait instability. Age-related changes to tendon stiffness may also delay muscle stretch and afferent feedback and decrease force transmission, worsening fall outcomes. However, the association between muscle strength, tendon stiffness, and gait instability is not well established. Given the ankle's proximity to the onset of many walking balance disturbances, we examined the relation between both plantarflexor strength and Achilles tendon stiffness with walking-related instability during perturbed gait in older and younger adults-the latter quantified herein using margins of stability and whole-body angular momentum including the application of treadmill-induced slip perturbations. Older and younger adults did not differ in plantarflexor strength, but Achilles tendon stiffness was lower in older adults. Among older adults, plantarflexor weakness associated with greater whole-body angular momentum following treadmill-induced slip perturbations. Weaker older adults also appeared to walk and recover from treadmill-induced slip perturbations with more caution. This study highlights the role of plantarflexor strength and Achilles tendon stiffness in regulating lateral gait stability in older adults, which may be targets for training protocols seeking to minimize fall risk and injury severity.


Asunto(s)
Tendón Calcáneo , Trastornos Neurológicos de la Marcha , Humanos , Anciano , Marcha/fisiología , Caminata/fisiología , Envejecimiento/fisiología , Fenómenos Mecánicos , Tendón Calcáneo/fisiología , Equilibrio Postural , Fenómenos Biomecánicos
2.
J Biomech ; 164: 111984, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38330884

RESUMEN

Running studies, particularly those examining footwear effects, commonly use warm-up or familiarization periods prior to testing. There is no consensus for how long these familiarization periods should be to ensure stable running kinematics prior to experimental testing in novel footwear. The aim of this study was to assess the time to stability of kinematic variables during treadmill running in novel compared to habitual neutral cushion footwear in distance runners. A cross-sectional analysis of 15 distance runners (seven women, eight men) during 10-minute treadmill running bouts in minimal, neutral cushion, and maximal cushioned footwear was conducted while lower extremity kinematics were recorded for 10 s at the end of each minute. Test-retest intra-class correlation coefficients (ICC, 3, k) were used to detect time to stability in cadence, vertical oscillation, peak dorsiflexion angle, peak eversion angle, and peak knee flexion angle. All kinematic variables were stabilized within two to three minutes (ICC < 0.90) and the type of novel footwear did not influence time to stability. These findings indicate that a two to three minute, ∼310-540 steps, depending on running cadence, familiarization period, regardless of footwear novelty, is sufficient for stabilization of these kinematic variables during treadmill running.


Asunto(s)
Carrera , Zapatos , Masculino , Humanos , Femenino , Fenómenos Biomecánicos , Estudios Transversales , Extremidad Inferior
3.
Artículo en Inglés | MEDLINE | ID: mdl-38378242

RESUMEN

OBJECTIVES: This study examined the effects of virtual reality (VR) among palliative care patients at an acute ward. Objectives included evaluating VR therapy benefits across three sessions, assessing its differential impact on emotional versus physical symptoms and determining the proportion of patients experiencing clinically meaningful improvements after each session. METHODS: A mixed-methods design was employed. Sixteen palliative inpatients completed three personalised 20 min VR sessions. Symptom burden was assessed using the Edmonton Symptom Assessment Scale-Revised and quality of life with the Functional Assessment of Chronic Illness Therapy (FACIT-Pal-14). Standardised criteria assessed clinically meaningful changes. Quantitative data were analysed using linear mixed models. RESULTS: Quality of life improved significantly pre-VR to post-VR with a large effect size (Cohen's d: 0.98). Total symptom burden decreased after 20 min VR sessions (Cohen's d: 0.75), with similar effect sizes for emotional (Cohen's d: 0.67) and physical symptoms (Cohen's d: 0.63). Over 50% of patients experienced clinically meaningful improvements per session, though substantial individual variability occurred. CONCLUSIONS: This study reveals the nuanced efficacy of personalised VR therapy in palliative care, with over half of the patients experiencing meaningful benefits in emotional and physical symptoms. The marked variability in responses underscores the need for realistic expectations when implementing VR therapy.

4.
Integr Environ Assess Manag ; 20(1): 148-158, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37166226

RESUMEN

The Fundão mine tailings dam rupture of 2015, in the Rio Doce basin, Brazil, resulted in the deposition of tailings downstream of the dam. It has yet to be determined if metals associated with the tailings have contributed toxicity to organisms, burying a time bomb that could be ticking. Currently the data on toxicity to benthic and aquatic organisms have not been assessed sufficiently to allow an informed assessment using an approach based on weight-of-evidence. This study was conducted to ascertain if sediments at "hot spots" that received Fundão tailings reflected elevated concentrations of metals and if these concentrations were sufficient to result in toxicity to freshwater organisms. The lines-of-evidence considered included assessing metals concentrations in relation to sediment quality criteria, establishing biogeochemical characterizations, completing an evaluation of potential metal release upon resuspension to provide information on bioavailability, and identifying acute and chronic toxicity effects using sensitive native species for waters (water flea, Daphnia similis) and sediments (burrowing midge larvae, Chironomus sancticaroli). Only porewater concentrations of iron and manganese exceeded Brazilian surface water criteria, whereas most trace elements exhibited no enrichment or elevated environmental indexes. The concentrations of bioavailable metals were assessed to be low, and metal concentrations did not increase in the overlying water upon resuspension; rather, they decreased through time. Toxicity testing in resuspended waters and bulk sediments resulted in no acute or chronic toxicity to either benthic or aquatic species. The low metal bioavailability and absence of toxicity of the tailings-enriched sediments was attributed to the strong binding and rapid removal of potentially toxic metal ions caused by oxyhydroxides and particles in the presence of iron-rich particulates. The findings of these sediment hot-spot studies indicate the Fundão dam release of tailings more than six years ago is not causing the current release of toxic concentrations of metals into the freshwaters of the Rio Doce. Integr Environ Assess Manag 2024;20:148-158. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Asunto(s)
Oligoelementos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Metales/toxicidad , Metales/análisis , Hierro , Brasil
5.
Integr Environ Assess Manag ; 20(1): 70-73, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38037522

RESUMEN

The second Fundão Dam Rupture Science Meeting was held in Ouro Preto, Minas Gerais, Brazil, on 21 and 22 September 2022. A total of 100 delegates attended the meeting, which featured high-quality oral presentations and posters over the two days and lively discussions of the science presented. The meeting resulted in nine papers being published in this special series. In the discussion, it was commented that the first meeting had been more a meeting of competitive perspectives but that the second meeting featured a more collaborative sharing of knowledge. Also, there had been substantial improvement in ways to deal with the lack of pre-event data and account for other stressors in the system, and as a result, stronger conclusions regarding the recovery rates of the system were able to be made. Importantly, there was no evidence for a feasible "time bomb" of a future catastrophic release of contaminants, but it was agreed that different scenarios continue to be researched. Integr Environ Assess Manag 2024;20:70-73. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Asunto(s)
Ecotoxicología , Monitoreo del Ambiente , Ecotoxicología/métodos , Brasil , Monitoreo del Ambiente/métodos
6.
PeerJ ; 11: e16095, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810786

RESUMEN

Background: How we feel during exercise is influenced by exteroceptive (e.g., vision) and interoceptive (i.e., internal body signals) sensory information, and by our prior experiences and expectations. Deceptive visual cues about one's performance during exercise can increase work rate, without negatively impacting affective valence (good/bad responses) or perceived exertion. However, what is less understood is whether the perception of the exercise experience itself can be shifted, if work rate is held constant. Here we aimed to investigate whether deceptive vision-via illusory hills in a virtual reality (VR) cycling experience-alters affective valence and perceived exertion when physical effort is controlled. We also evaluated whether the accuracy with which one detects interoceptive cues influences the extent to which deceptive visual information can shift exercise experiences. Methods: A total of 20 participants (10 female; 30.2 ± 11.2 yrs) completed three VR cycling conditions each of 10-min duration, in a randomised, counterbalanced order. Pedal resistance/cadence were individualised (to exercise intensity around ventilatory threshold) and held constant across conditions; only visual cues varied. Two conditions provided deceptive visual cues about the terrain (illusory uphill, illusory downhill; resistance did not change); one condition provided accurate visual cues (flat terrain). Ratings of affective valence (Feeling Scale) and of perceived exertion (Borg's RPE) were obtained at standardised timepoints in each VR condition. Interoceptive accuracy was measured via a heartbeat detection test. Results: Linear mixed effects models revealed that deceptive visual cues altered affective valence (f2 = 0.0198). Relative to flat terrain, illusory downhill reduced affective valence (Est = -0.21, p = 0.003), but illusory uphill did not significantly improve affective valence (Est = 0.107, p = 0.14). Deceptive visual cues altered perceived exertion, and this was moderated by the level of interoceptive accuracy (Condition-Interoception interaction, p = 0.00000024, f2 = 0.0307). Higher levels of interoceptive accuracy resulted in higher perceived exertion in the illusory downhill condition (vs flat), while lower interoceptive accuracy resulted in lower perceived exertion in both illusory hill conditions (vs flat) and shifts of greater magnitude. Conclusions: Deceptive visual cues influence perceptual responses during exercise when physical effort does not vary, and for perceived exertion, the weighting given to visual exteroceptive cues is determined by accuracy with which interoceptive cues are detected. Contrary to our hypotheses, deceptive visual cues did not improve affective valence. Our findings suggest that those with lower levels of interoceptive accuracy experience most benefit from deceptive visual cues, providing preliminary insight into individualised exercise prescription to promote positive (and avoid negative) exercise experiences.


Asunto(s)
Ilusiones , Interocepción , Humanos , Femenino , Señales (Psicología) , Ejercicio Físico/fisiología , Esfuerzo Físico/fisiología , Emociones , Interocepción/fisiología
7.
JMIR Hum Factors ; 10: e34629, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37494096

RESUMEN

BACKGROUND: Interactive, mixed reality technologies such as augmented reality, virtual reality, and holographic technology may provide a novel solution to fast-track the translation of evidence into practice. They may also help overcome barriers to both mental health and asthma management service uptake, such as cost, availability of appointments, fear of judgment, and quality of care. OBJECTIVE: This study aimed to investigate if mixed reality technology is an acceptable mechanism for the delivery of a component of cognitive and behavioral therapies for the management of elevated psychological distress among young people with asthma. METHODS: To explore the perceived acceptability of these technologies, mixed reality tools were evaluated via qualitative, 1-on-1 interviews with young people with asthma and symptoms of psychological distress, parents/caregivers of young people with asthma and symptoms of psychological distress, and relevant health professionals. The Theoretical Framework of Acceptability was used for the deductive coding of the recorded interview transcripts. RESULTS: This study enrolled the following participants: (1) 3 adolescents with asthma and symptoms of psychological distress with a mean age of 14 (SD 1.7) years; (2) 4 parents/caregivers of adolescents with asthma with a mean age of 55 (SD 14.6) years; and (3) 6 health professionals with a mean age of 40.8 (SD 4.3) years. A total of 4 constructs-experienced affective attitude, experienced effectiveness, self-efficacy, and intervention coherence-were coded in all participant transcripts. The most frequently coded constructs were experienced affective attitude and intervention coherence, which were reported a total of 96 times. The least frequently coded construct was anticipated opportunity cost, which was reported a total of 5 times. Participants were mostly positive about the mixed reality resources. However, some concerns were raised regarding ethicality, particularly regarding privacy, accessibility, and messaging. Participants noted the need for technology to be used in conjunction with face-to-face engagement with health professionals and that some patients would respond to this type of delivery mechanism better than others. CONCLUSIONS: These results suggest that mixed reality technology to deliver psychological interventions may be an acceptable addition to current health care practices for young people with asthma and symptoms of psychological distress. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12620001109998; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380427.

8.
Analyst ; 148(14): 3226-3238, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37326420

RESUMEN

The THermally Evaporated Spray for Engineered Uniform particulateS (THESEUS) production platform was developed to generate highly uniform mixed actinide oxide particles. The particulate synthesis platform builds on previous efforts and utilizes an aerosol-based technology to generate, calcine, characterize, and aggregate a monodisperse oxide phase particle product. In this study, particles comprised of uranium oxide, incorporated with varying compositions of thorium, were produced. Th/U test materials with 232Th concentrations between 1 ppm and 10%, ratioed to 238U, were successfully generated with in situ calcination at 600 °C and characterized by in situ aerodynamic particle size spectrometry and ex situ microanalytical methods. Populations of monodisperse particulates (geometric standard deviation - GSD < 1.15) with an average diameter near 1 µm were generatated and micro-Raman spectroscopy of individual particles identified U3O8 as the primary material phase for the range of Th/U samples analyzed. Single particle measurements and automated particle analyses by secondary ion mass spectrometry (SIMS) were performed. Uniform inter-particle elemental and isotopic homogeneity for uranium and thorium isotopes was characterized by SIMS, and a 232Th/238U relative sensitivity factor of 0.53 was determined. SIMS results demonstrated differences in the 232Th/238U profiling behavior for Th/U particulates with increased Th content (>1%). Despite the observed profiling behavior, single particle measurements of the 10% Th sample indicate inter-particle homogeneity. This work represents the first systematic study of Th/U microparticulate reference materials generated and intended for nuclear safeguards applications and serves as a demonstration of THESEUS to support a sustained capability for the production mixed-element particulate reference materials.

10.
IEEE Trans Vis Comput Graph ; 29(2): 1478-1490, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34653001

RESUMEN

This article presents a set of adaptive reset techniques for use with haptic retargeting systems focusing on interaction with hybrid virtual reality interfaces that align with a physical interface. Haptic retargeting between changing physical and virtual targets requires a reset where the physical and virtual hand positions are re-aligned. We present a modified Point technique to guide the user in the direction of their next interaction such that the remaining distance to the target is minimized upon completion of the reset. This, along with techniques drawn from existing work are further modified to consider the angular and translational gain of each redirection and identify the optimal position for the reset to take place. When the angular and translational gain is within an acceptable range, the reset can be entirely omitted. This enables continuous retargeting between targets removing interruptions from a sequence of retargeted interactions. These techniques were evaluated in a user study which showed that adaptive reset techniques can provide a significant decrease in task completion time, travel distance, and the number of user errors.

11.
Environ Toxicol Chem ; 42(2): 303-316, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36416265

RESUMEN

The toxicity of iron(III) in fresh waters has been detected at concentrations above the iron solubility limit, indicating a contribution of colloidal and particulate forms of iron(III) to the toxicity response. Current water quality guideline values for iron in fresh water are based on analytical determinations of filterable or total iron. Filtration, however, can underestimate bioavailable iron by retaining some of the colloidal fraction, and total determinations overestimate bioavailable iron measurements by recovering fractions of low bioavailability from suspended solids (e.g., iron oxides and oxyhydroxides) naturally abundant in many surface waters. Consequently, there is a need for an analytical method that permits the determination of a bioavailable iron fraction, while avoiding false-negative and false-positive results. Ideally, a measurement technique is required that can be readily applied by commercial laboratories and field sampling personnel, and integrated into established regulatory schemes. The present study investigated the performance of pH 2 and pH 4 extractions to estimate a bioavailable iron(III) fraction in synthetic water samples containing iron phases of different reactivities. The effects of aging on fresh precipitates were also studied. The total recoverable, 0.45-µm filtered, and pH 4 extractable fractions did not discriminate iron phases and age groups satisfactorily. Contrastingly, the pH 2 extraction showed specificity toward iron phases and aging (0.5-2-h interval). Extraction times above 4 h and up to 16 h equally recovered >90% of the spiked iron regardless of its age. Furthermore, <1% of the well-mineralized iron was targeted. The present study shows that a pH 2 dilute-acid extraction is a suitable candidate method to operationally define iron fractions of higher bioavailability avoiding false-negative and false-positive results. Environ Toxicol Chem 2023;42:303-316. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Asunto(s)
Hierro , Contaminantes Químicos del Agua , Compuestos Férricos , Disponibilidad Biológica , Agua Dulce , Calidad del Agua , Contaminantes Químicos del Agua/toxicidad
12.
J Sport Health Sci ; 12(5): 639-647, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-35872091

RESUMEN

BACKGROUND: During human locomotion, a sufficiently stiff foot allows the ankle plantar flexors to generate large propulsive powers. Increasing foot stiffness (e.g., via a carbon plate) increases the ankle's external moment arm in relation to the internal moment arm (i.e., increasing gear ratio), reduces plantar flexor muscles' shortening velocity, and enhances muscle force production. In contrast, when activation of the foot's intrinsic muscles is impaired, there is a reduction in foot and ankle work and metatarsophalangeal joint stiffness. We speculated that the reduced capacity to actively control metatarsophalangeal joint stiffness may impair the gearing function of the foot at the ankle. METHODS: We used a tibial nerve block to examine the direct effects of the intrinsic foot muscles on ankle joint kinetics, in vivo medial gastrocnemius' musculotendinous dynamics, and ankle gear ratio on 14 participants during maximal vertical jumping. RESULTS: Under the nerve block, the internal ankle plantar flexion moment decreased (p = 0.004) alongside a reduction in external moment arm length (p = 0.021) and ankle joint gear ratio (p = 0.049) when compared to the non-blocked condition. Although medial gastrocnemius muscle-tendon unit and fascicle velocity were not different between conditions, the Achilles tendon was shorter during propulsion in the nerve block condition (p < 0.001). CONCLUSION: In addition to their known role of regulating the energetic function of the foot, our data indicate that the intrinsic foot muscles also act to optimize ankle joint torque production and leverage during the propulsion phase of vertical jumping.


Asunto(s)
Articulación del Tobillo , Músculo Esquelético , Humanos , Músculo Esquelético/fisiología , Tobillo/fisiología , Caminata/fisiología , Marcha/fisiología
13.
Int J Mol Sci ; 23(20)2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36293431

RESUMEN

Cerebral cavernous malformation (CCM) is a neurovascular disease that affects 0.5% of the general population. For a long time, CCM research focused on genetic mutations, endothelial junctions and proliferation, but recently, transcriptome and proteome studies have revealed that the hemostatic system and neuroinflammation play a crucial role in the development and severity of cavernomas, with some of these publications coming from our group. The aim of this review is to give an overview of the latest molecular insights into the interaction between CCM-deficient endothelial cells with blood components and the neurovascular unit. Specifically, we underscore how endothelial dysfunction can result in dysregulated hemostasis, bleeding, hypoxia and neurological symptoms. We conducted a thorough review of the literature and found a field that is increasingly poised to regard CCM as a hemostatic disease, which may have implications for therapy.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Hemostáticos , Humanos , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Células Endoteliales , Tromboinflamación , Proteoma , Hemostasis
14.
PLoS One ; 17(9): e0272343, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36070284

RESUMEN

Reallocations of time between daily activities such as sleep, sedentary behavior and physical activity are differentially associated with markers of physical, mental and social health. An individual's most desirable allocation of time may differ depending on which outcomes they value most, with these outcomes potentially competing with each other for reallocations. We aimed to develop an interactive app that translates how self-selected time reallocations are associated with multiple health measures. We used data from the Australian Child Health CheckPoint study (n = 1685, 48% female, 11-12 y), with time spent in daily activities derived from a validated 24-h recall instrument, %body fat from bioelectric impedance, psychosocial health from the Pediatric Quality of Life Inventory and academic performance (writing) from national standardized tests. We created a user-interface to the compositional isotemporal substitution model with interactive sliders that can be manipulated to self-select time reallocations between activities. The time-use composition was significantly associated with body fat percentage (F = 2.66, P < .001), psychosocial health (F = 4.02, P < .001), and academic performance (F = 2.76, P < .001). Dragging the sliders on the app shows how self-selected time reallocations are associated with the health measures. For example, reallocating 60 minutes from screen time to physical activity was associated with -0.8 [95% CI -1.0 to -0.5] %body fat, +1.9 [1.4 to 2.5] psychosocial score and +4.5 [1.8 to 7.2] academic performance. Our app allows the health associations of time reallocations to be compared against each other. Interactive interfaces provide flexibility in selecting which time reallocations to investigate, and may transform how research findings are disseminated.


Asunto(s)
Aplicaciones Móviles , Calidad de Vida , Australia , Niño , Ejercicio Físico , Femenino , Humanos , Masculino , Conducta Sedentaria
15.
Small ; 18(39): e2203918, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36047959

RESUMEN

Iron oxide (Fe2 O3 ) is an abundant and potentially low-cost material for fabricating lithium-ion battery anodes. Here, the growth of α-Fe2 O3 nano-flowers at an electrified liquid-liquid interface is demonstrated. Sonication is used to convert these flowers into quasi-2D platelets with lateral sizes in the range of hundreds of nanometers and thicknesses in the range of tens of nanometers. These nanoplatelets can be combined with carbon nanotubes to form porous, conductive composites which can be used as electrodes in lithium-ion batteries. Using a standard activation process, these anodes display good cycling stability, reasonable rate performance and low-rate capacities approaching 1500 mAh g-1 , consistent with the current state-of-the-art for Fe2 O3 . However, by using an extended activation process, it is found that the morphology of these composites can be significantly changed, rendering the iron oxide amorphous and significantly increasing the porosity and internal surface area. These morphological changes yield anodes with very good cycling stability and low-rate capacity exceeding 2000 mAh g-1 , which is competitive with the best anode materials in the literature. However, the data implies that, after activation, the iron oxide displays a reduced solid-state lithium-ion diffusion coefficient resulting in somewhat degraded rate performance.

16.
Blood ; 140(20): 2154-2169, 2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-35981497

RESUMEN

Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Humanos , Animales , Ratones , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Células Endoteliales/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Tromboinflamación , Factor de von Willebrand/metabolismo , Hipoxia/metabolismo
19.
Cell Mol Life Sci ; 79(4): 206, 2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35333979

RESUMEN

Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3iECKO), we show that endothelial cells from Ccm3iECKO mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3iECKO mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3iECKO mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas  of patients with CCM confirms the clinical relevance of NETs in CCM.


Asunto(s)
Trampas Extracelulares , Hemangioma Cavernoso del Sistema Nervioso Central , Animales , Proteínas Reguladoras de la Apoptosis/genética , Células Endoteliales/metabolismo , Trampas Extracelulares/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Inflamación/patología , Proteínas de la Membrana/metabolismo , Ratones
20.
J Exp Biol ; 225(8)2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35344050

RESUMEN

The central nervous system utilizes tendon compliance of the intrinsic foot muscles to aid the foot's arch spring, storing and returning energy in its tendinous tissues. Recently, the intrinsic foot muscles have been shown to adapt their energetic contributions during a variety of locomotor tasks to fulfil centre of mass work demands. However, the mechanism by which the small intrinsic foot muscles are able to make versatile energetic contributions remains unknown. Therefore, we examined the muscle-tendon dynamics of the flexor digitorum brevis during stepping, jumping and landing tasks to see whether the central nervous system regulates muscle activation magnitude and timing to enable energy storage and return to enhance energetic contributions. In step-ups and jumps, energy was stored in the tendinous tissue during arch compression; during arch recoil, the fascicles shortened at a slower rate than the tendinous tissues while the foot generated energy. In step-downs and landings, the tendinous tissues elongated more and at greater rates than the fascicles during arch compression while the foot absorbed energy. These results indicate that the central nervous system utilizes arch compression to store elastic energy in the tendinous tissues of the intrinsic foot muscles to add or remove mechanical energy when the body accelerates or decelerates. This study provides evidence for an adaptive mechanism to enable the foot's energetic versatility and further indicates the value of tendon compliance in distal lower limb muscle-tendon units in locomotion.


Asunto(s)
Pie , Músculo Esquelético , Fenómenos Biomecánicos , Pie/fisiología , Locomoción , Músculo Esquelético/fisiología , Tendones/fisiología
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