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1.
Exp Brain Res ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38949687

RESUMO

BACKGROUND: The frontal cortex, relevant to global cognition and motor function, is recruited to compensate for mobility dysfunction in older adults. However, the in vivo neurophysiological (e.g., neurometabolites) underpinnings of the frontal cortex compensation for mobility dysfunction remain poorly understood. The purpose of this study was to investigate the relationships among frontal cortex neurophysiology, mobility, and cognition in healthy older adults. METHODS: Magnetic Resonance Spectroscopy (MRS) quantified N-acetylasparate (tNAA) and total choline (tCho) concentrations and ratios in the frontal cortex in 21 older adults. Four inertial sensors recorded the Timed Up & Go (TUG) test. Cognition was assessed using the Flanker Inhibitory Control and Attention Test which requires conflict resolution because of response interference from flanking distractors during incongruent trials. Congruent trials require no conflict resolution. RESULTS: tNAA concentration significantly related to the standing (p = 0.04) and sitting (p = 0.03) lean angles. tCho concentration (p = 0.04) and tCho ratio (p = 0.02) significantly related to TUG duration. tCho concentration significantly related to incongruent response time (p = 0.01). tCho ratio significantly related to both congruent (p = 0.009) and incongruent (p < 0.001) response times. Congruent (p = 0.02) and incongruent (p = 0.02) Flanker response times significantly related to TUG duration. CONCLUSIONS: Altered levels of frontal cortex neurometabolites are associated with both mobility and cognitive abilities in healthy older adults. Identifying neurometabolites associated with frontal cortex compensation of mobility dysfunction could improve targeted therapies aimed at improving mobility in older adults.

2.
J Robot Surg ; 18(1): 278, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960985

RESUMO

Historically, pedicle screw accuracy measurements have relied on CT and expert visual assessment of the position of pedicle screws relative to preoperative plans. Proper pedicle screw placement is necessary to avoid complications, cost and morbidity of revision procedures. The aim of this study was to determine accuracy and precision of pedicle screw insertion via a novel computer vision algorithm using preoperative and postoperative computed tomography (CT) scans. Three cadaveric specimens were utilized. Screw placement planning on preoperative CT was performed according to standard clinical practice. Two experienced surgeons performed bilateral T2-L4 instrumentation using robotic-assisted navigation. Postoperative CT scans of the instrumented levels were obtained. Automated segmentation and computer vision techniques were employed to align each preoperative vertebra with its postoperative counterpart and then compare screw positions along all three axes. Registration accuracy was assessed by preoperatively embedding spherical markers (tantalum beads) to measure discrepancies in landmark alignment. Eighty-eight pedicle screws were placed in 3 cadavers' spines. Automated registrations between pre- and postoperative CT achieved sub-voxel accuracy. For the screw tip and tail, the mean three-dimensional errors were 1.67 mm and 1.78 mm, respectively. Mean angular deviation of screw axes from plan was 1.58°. For screw mid-pedicular accuracy, mean absolute error in the medial-lateral and superior-inferior directions were 0.75 mm and 0.60 mm, respectively. This study introduces automated algorithms for determining accuracy and precision of planned pedicle screws. Our accuracy outcomes are comparable or superior to recent robotic-assisted in vivo and cadaver studies. This computerized workflow establishes a standardized protocol for assessing pedicle screw placement accuracy and precision and provides detailed 3D translational and angular accuracy and precision for baseline comparison.


Assuntos
Algoritmos , Cadáver , Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Tomografia Computadorizada por Raios X , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Cirurgia Assistida por Computador/métodos
3.
Methods Mol Biol ; 2814: 1-27, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954194

RESUMO

The social amoeba Dictyostelium discoideum is a versatile model for understanding many different cellular processes involving cell motility including chemotaxis, phagocytosis, and cytokinesis. Cytokinesis, in particular, is a model cell-shaped change process in which a cell separates into two daughter cells. D. discoideum has been used extensively to identify players in cytokinesis and understand how they comprise the mechanosensory and biochemical pathways of cytokinesis. In this chapter, we describe how we use cDNA library complementation with D. discoideum to discover potential regulators of cytokinesis. Once identified, these regulators are further analyzed through live cell imaging, immunofluorescence imaging, fluorescence correlation and cross-correlation spectroscopy, micropipette aspiration, and fluorescence recovery after photobleaching. Collectively, these methods aid in detailing the mechanisms and signaling pathways that comprise cell division.


Assuntos
Citocinese , Dictyostelium , Dictyostelium/metabolismo , Dictyostelium/genética , Dictyostelium/citologia , Biblioteca Gênica , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Transdução de Sinais , Recuperação de Fluorescência Após Fotodegradação/métodos
4.
Sci Adv ; 10(24): eadk9731, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38865458

RESUMO

Nonlinear biomolecular interactions on membranes drive membrane remodeling crucial for biological processes including chemotaxis, cytokinesis, and endocytosis. The complexity of biomolecular interactions, their redundancy, and the importance of spatiotemporal context in membrane organization impede understanding of the physical principles governing membrane mechanics. Developing a minimal in vitro system that mimics molecular signaling and membrane remodeling while maintaining physiological fidelity poses a major challenge. Inspired by chemotaxis, we reconstructed chemically regulated actin polymerization inside vesicles, guiding membrane self-organization. An external, undirected chemical input induced directed actin polymerization and membrane deformation uncorrelated with upstream biochemical cues, suggesting symmetry breaking. A biophysical model incorporating actin dynamics and membrane mechanics proposes that uneven actin distributions cause nonlinear membrane deformations, consistent with experimental findings. This protocellular system illuminates the interplay between actin dynamics and membrane shape during symmetry breaking, offering insights into chemotaxis and other cell biological processes.


Assuntos
Actinas , Células Artificiais , Membrana Celular , Polimerização , Actinas/metabolismo , Células Artificiais/metabolismo , Células Artificiais/química , Membrana Celular/metabolismo , Quimiotaxia , Modelos Biológicos
5.
bioRxiv ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38854143

RESUMO

Older adults and neurological populations tend to walk with slower speeds, more gait variability, and a higher metabolic cost. This higher metabolic cost could be related to their increased gait variability, but this relationship is still unclear. The purpose of this study was to determine how increased step length variability affects the metabolic cost of waking. Eighteen healthy young adults completed a set of 5-minute trials of treadmill walking at 1.20 m/s while we manipulated their step length variability. Illuminated rectangles were projected onto the surface of a treadmill to cue step length variabilities of 0, 5 and 10% (coefficient of variation). Actual step lengths and their variability were tracked with reflective markers on the feet, while metabolic cost was measured using indirect calorimetry. Changes in metabolic cost across habitual walking (no projections) and the three variability conditions were analyzed using a linear mixed effects model. Metabolic power was largest in the 10% condition (4.30 ± 0.23 W/kg) compared to 0% (4.16 ± 0.18 W/kg) and habitual (3.98 ± 0.25 W/kg). The participant's actual step length variability did not match projected conditions for 0% (3.10%) and 10% (7.03%). For every 1% increase in step length variability, there is an 0.7% increase in metabolic cost. Our results demonstrate an association between the metabolic cost of walking and gait step length variability. This suggests that increased gait variability contributes to a portion of the increased cost of walking seen in older adults and neurological populations.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38709012

RESUMO

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the change in angle of trunk rotation (ATR), axial vertebral rotation (AVR), and body surface rotation (BSR) in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with en-bloc derotation across multiple postoperative visits. SUMMARY OF BACKGROUND DATA: Previous research has documented ATR, AVR, and BSR correction for AIS patients after surgery. However, there is a lack of evidence on the sustainability of this correction over time. METHODS: This was a retrospective study from a single-center prospective surface topographic registry of patients with AIS, age 11-20 at time of surgery, who underwent PSF with en-bloc derotation. Patients with previous spine surgery were excluded. ATR was measured with a scoliometer, AVR through EOS radiographic imaging, and BSR via surface topographic scanning, Data collection occurred at: preoperative, six-week, three-month, six-month, one-year, and two-year postoperative visits. BSR and AVR were tracked at the preoperative apical vertebral level, and the level with maximum deformity, at each respective timepoint. Generalized estimating equations models were used for statistical analysis. Covariates included age, sex, and body mass index. RESULTS: 49 patients (73.4% female, mean age 14.6±2.2 years, mean preoperative coronal curve angle 57.9°±8.5, and 67% major thoracic) were evaluated. ATR correction was significantly improved at all postoperative timepoints and there was no significant loss of correction. AVR Max and AVR Apex were significantly improved at all timepoints but there was a significant loss of correction for AVR Apex between the six-week and one-year visit (P=0.032). BSR Max achieved significant improvement at the three-month visit. BSR Apex was significantly improved at the three-month and one-year visit. CONCLUSION: ATR and AVR demonstrated significant axial plane correction at two-years postoperative in patients undergoing PSF for AIS. BSR did not maintain significant improvement by the two-year visit.

7.
Dev Cogn Neurosci ; 67: 101385, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38713999

RESUMO

INTRODUCTION: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. METHODS: Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. RESULTS: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. CONCLUSIONS: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.


Assuntos
Vermis Cerebelar , Cognição , Imageamento por Ressonância Magnética , Humanos , Adolescente , Criança , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Cognição/fisiologia , Adulto , Adulto Jovem , Vermis Cerebelar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/anatomia & histologia
8.
Sci Transl Med ; 16(745): eadj4303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38691619

RESUMO

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.


Assuntos
Tronco Encefálico , Estado de Consciência , Imageamento por Ressonância Magnética , Vigília , Humanos , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/fisiologia , Vigília/fisiologia , Estado de Consciência/fisiologia , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Conectoma , Vias Neurais/fisiologia , Masculino , Feminino , Imagem de Difusão por Ressonância Magnética , Adulto , Nível de Alerta/fisiologia
9.
Pharmacy (Basel) ; 12(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38668086

RESUMO

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

10.
Metabolites ; 14(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38668305

RESUMO

In the context of dietary transition toward plant proteins, it is necessary to ensure protein security in populations. It would thus be of interest to identify biomarkers of altered protein digestibility in populations. We examined the association between urinary metabolites and the acute intake of low- or highly digestible protein in healthy volunteers. The urine samples were collected before and 9 h after the ingestion of a meal containing either no protein, zein (low-digestible) or whey protein isolate (highly digestible). The liquid chromatography-high resolution mass spectrometry metabolomics approach was used for the profiling of the urinary metabolites. For the standardization of metabolomics data sets, osmolality-based, standard normal variates (SNV) and probabilistic quotient normalization (PQN) techniques were used. The ANOVA-based factorial method, AComDim_ICA, was used for chemometrics analysis. The osmolality adjustment has a beneficial effect and the subsequent mathematical normalization improves the chemometric analysis further. Some changes in the urinary metabolomes were observed 9 h after the meal in the three groups. However, there was no difference in the urine metabolome between groups. No biomarker of protein digestibility can be identified after the ingestion of a single meal, even when marked differences in the digestion efficiency of protein have been observed.

11.
Proc Natl Acad Sci U S A ; 121(19): e2313568121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38648470

RESUMO

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.


Assuntos
Traumatismos por Explosões , Militares , Humanos , Traumatismos por Explosões/diagnóstico por imagem , Adulto , Masculino , Estados Unidos , Imageamento por Ressonância Magnética , Feminino , Tomografia por Emissão de Pósitrons , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Adulto Jovem
12.
Antimicrob Agents Chemother ; 68(5): e0018224, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38597672

RESUMO

Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50-75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration (fT >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin (n = 15) and cefadroxil (n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil's longer half-life (1.61 h) than cephalexin's (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.


Assuntos
Antibacterianos , Cefadroxila , Cefalexina , Estudos Cross-Over , Testes de Sensibilidade Microbiana , Cefalexina/farmacocinética , Cefalexina/uso terapêutico , Humanos , Criança , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Cefadroxila/farmacocinética , Cefadroxila/uso terapêutico , Feminino , Masculino , Pré-Escolar , Adolescente , Lactente , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
13.
Neurorehabil Neural Repair ; 38(5): 364-372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38506532

RESUMO

BACKGROUND: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics. METHODS: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO2]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group. RESULTS: Average NSI total score was 26.4 (13.2). HbO2 was significantly higher (P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion (r = .79; P = .001), and stride time variability (r = -.54; P = .046). CONCLUSION: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms.


Assuntos
Concussão Encefálica , Síndrome Pós-Concussão , Córtex Pré-Frontal , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Masculino , Feminino , Adulto , Concussão Encefálica/fisiopatologia , Concussão Encefálica/complicações , Adulto Jovem , Síndrome Pós-Concussão/fisiopatologia , Síndrome Pós-Concussão/etiologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Pessoa de Meia-Idade , Marcha/fisiologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-38520148

RESUMO

The cell's ability to change shape is a central feature in many cellular processes, including cytokinesis, motility, migration, and tissue formation. The cell constructs a network of contractile proteins underneath the cell membrane to form the cortex, and the reorganization of these components directly contributes to cellular shape changes. The desire to mimic these cell shape changes to aid in the creation of a synthetic cell has been increasing. Therefore, membrane-based reconstitution experiments have flourished, furthering our understanding of the minimal components the cell uses throughout these processes. Although biochemical approaches increased our understanding of actin, myosin II, and actin-associated proteins, using membrane-based reconstituted systems has further expanded our understanding of actin structures and functions because membrane-cortex interactions can be analyzed. In this review, we highlight the recent developments in membrane-based reconstitution techniques. We examine the current findings on the minimal components needed to recapitulate distinct actin structures and functions and how they relate to the cortex's impact on cellular mechanical properties. We also explore how co-processing of computational models with wet-lab experiments enhances our understanding of these properties. Finally, we emphasize the benefits and challenges inherent to membrane-based, reconstitution assays, ranging from the advantage of precise control over the system to the difficulty of integrating these findings into the complex cellular environment.

15.
bioRxiv ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38405988

RESUMO

To move through complex environments, cells must constantly integrate chemical and mechanical cues. Signaling networks, such as those comprising Ras and PI3K, transmit chemical cues to the cytoskeleton, but the cytoskeleton must also relay mechanical information back to those signaling systems. Using novel synthetic tools to acutely control specific elements of the cytoskeleton in Dictyostelium and neutrophils, we delineate feedback mechanisms that alter the signaling network and promote front- or back-states of the cell membrane and cortex. First, increasing branched actin assembly increases Ras/PI3K activation while reducing polymeric actin levels overall decreases activation. Second, reducing myosin II assembly immediately increases Ras/PI3K activation and sensitivity to chemotactic stimuli. Third, inhibiting branched actin alone increases cortical actin assembly and strongly blocks Ras/PI3K activation. This effect is mitigated by reducing filamentous actin levels and in cells lacking myosin II. Finally, increasing actin crosslinking with a controllable activator of cytoskeletal regulator RacE leads to a large decrease in Ras activation both globally and locally. Curiously, RacE activation can trigger cell spreading and protrusion with no detectable activation of branched actin nucleators. Taken together with legacy data that Ras/PI3K promotes branched actin assembly and myosin II disassembly, our results define front- and back-promoting positive feedback loops. We propose that these loops play a crucial role in establishing cell polarity and mediating signal integration by controlling the excitable state of the signal transduction networks in respective regions of the membrane and cortex. This interplay enables cells to navigate intricate topologies like tissues containing other cells, the extracellular matrix, and fluids.

16.
Heart Rhythm O2 ; 5(1): 24-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312200

RESUMO

Background: Catheter ablation of premature ventricular complexes (PVCs) and ventricular tachycardia (VT) from the left ventricular summit (LVS) may require advanced ablation techniques. Bipolar ablation from the coronary veins and adjacent endocardial structures can be effective for refractory LVS arrhythmias. Objective: The aim of this study was to investigate the outcomes of bipolar ablation performed between the coronary venous system and adjacent endocardial left ventricular outflow tract (LVOT) or right ventricular outflow tract (RVOT). Methods: This multicenter study included consecutive patients with LVS PVC/VT who underwent bipolar ablation between the anterior interventricular vein (AIV) or great cardiac vein (GCV) and the endocardial LVOT/RVOT after failed unipolar ablation. Ablation was started with powers of 10-20 W and uptitrated to achieve an impedance drop of at least 10%. Angiography was performed in all cases to confirm a safe distance (>5 mm) of the catheter from the major coronary arteries. Results: Between 2013 and 2023, bipolar radiofrequency ablation between the AIV/GCV and the adjacent LVOT/RVOT was attempted in 20 patients (4 female; age 57 ± 16 years). Unipolar ablation from sites of early activation (AIV/GCV, LVOT, aortic cusps, RVOT) failed to effectively suppress the PVC/VT in all subjects. Bipolar ablation was delivered with a maximum power of 30 ± 8 W and total duration of 238 ± 217 s and led to acute PVC/VT elimination in all patients. No procedural-related complications occurred. Over a follow-up period of 30 ± 24 months, the freedom from arrhythmia recurrence was 85% (1 recurrence in the VT group and 2 in the PVC group). PVC burden was reduced from 22% ± 10% to 4% ± 8% (P <.001). Conclusion: In cases of LVS PVC/VT refractory to unipolar ablation, bipolar ablation between the coronary venous system and adjacent endocardial LVOT/RVOT is safe and effective if careful titration of power and intraprocedural angiography are performed to ensure a safe distance from the coronary arteries.

17.
Europace ; 26(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305503

RESUMO

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Estenose de Veia Pulmonar , Humanos , Veias Pulmonares/cirurgia , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Método Simples-Cego , Resultado do Tratamento , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/etiologia
18.
PLoS One ; 19(2): e0288896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329957

RESUMO

The zero-velocity update (ZUPT) method has become a popular approach to estimate foot kinematics from foot worn inertial measurement units (IMUs) during walking and running. However, the accuracy of the ZUPT method for stride parameters at sprinting speeds remains unknown, specifically when using sensors with characteristics well suited for sprinting (i.e., high accelerometer and gyroscope ranges and sampling rates). Seventeen participants performed 80-meter track sprints while wearing a Blue Trident IMeasureU IMU. Two cameras, at 20 and 70 meters from the start, were used to validate the ZUPT method on a stride-by-stride and on a cumulative distance basis. In particular, the validity of the ZUPT method was assessed for: (1) estimating a single stride length attained near the end of an 80m sprint (i.e., stride at 70m); (2) estimating cumulative distance from ∼20 to ∼70 m; and (3) estimating total distance traveled for an 80-meter track sprint. Individual stride length errors at the 70-meter mark were within -6% to 3%, with a bias of -0.27%. Cumulative distance errors were within -4 to 2%, with biases ranging from -0.85 to -1.22%. The results of this study demonstrate the ZUPT method provides accurate estimates of stride length and cumulative distance traveled for sprinting speeds.


Assuntos
Corrida , Caminhada , Humanos , , Fenômenos Biomecânicos , Proteína Forkhead Box M1 , Marcha
19.
An Acad Bras Cienc ; 95(suppl 2): e20220573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198396

RESUMO

This study described the growth, morphometric, biomechanical, and chemical properties of the femur, tibiotarsus, and tarsometatarsus of European and Japanese quail. Analyses were performed at 13 and 15 days of incubation, at hatch, and at 4, 7, 10, 14, 21, 28, and 35 days post-hatch (n=6/subspecies/period). Bone specimens were analyzed by cone-beam computed tomography, biomechanical assays, chemical analyses, and histomorphometry. Variables were fitted by the Gompertz function and its derivative or assessed using the analysis of variance. Analysis of the derivative of Gompertz curves showed that the growth behavior of the tarsometatarsal bone was similar between quail subspecies, and the femur and tibiotarsus of European quail increased first in width and then in length, whereas the opposite occurred in Japanese quail. There was an interaction between quail subspecies and days of growth on femoral, tarsometatarsal, and tibiotarsal bone densities. Femoral and tibiotarsal cross-sectional areas were influenced by the interaction of quail subspecies and day of growth. Interaction effects were significant for breaking strength and phosphorus percentage. European and Japanese quail have different femoral and tibiotarsal growth patterns, especially in the first few days after hatching, whereas tarsometatarsal growth is similar between subspecies.


Assuntos
Coturnix , Codorniz , Animais , Fêmur/diagnóstico por imagem , Proliferação de Células , Bioensaio
20.
Orthop J Sports Med ; 12(1): 23259671231211885, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188621

RESUMO

Background: Quadriceps tendon autograft (QTA) has recently gained popularity in the treatment of anterior cruciate ligament (ACL) ruptures in pediatric patients. The addition of lateral extra-articular tenodesis (LET) to an ACL reconstruction (ACLR) has been found to reduce the risk of ACL retear in high-risk patients. Purpose: To (1) compare ACL graft maturity using signal intensity ratios (SIRs) on magnetic resonance imaging (MRI) scans in skeletally immature patients undergoing ACLR with QTA either with or without concomitant LET and (2) evaluate LET safety by calculating the physeal disturbance-related reoperation rate in the ACLR+LET group. Study Design: Cohort study; Level of evidence, 3. Methods: The records of patients aged ≤18 years who underwent ACLR between 2015 and 2021 were reviewed retrospectively. Patients undergoing ACLR with QTA who had open distal femoral and proximal tibial physes on MRI scans and a minimum 2-year follow-up data were included. SIR values were measured on sagittal MRI scans by averaging the signal at 3 regions of interest along the ACL graft and dividing by the signal of the posterior cruciate ligament at its insertion. Statistical analysis was performed to evaluate differences in SIR values at 6 months, 1 year, and 2 years postoperatively in patients who underwent ACLR alone versus ACLR+LET. Results: Overall, 29 patients were included in the study: 16 patients in the ACLR+LET group and 13 patients in the ACLR-only group. There were no significant differences in SIR values between groups at the 6-month or 1-year postoperative timepoints. At 2 years postoperatively, the median SIR of the ACLR+LET group was significantly lower than that of the ACLR-only group on both univariate (1.33 vs 1.86, respectively, P = .0012) and multivariate regression analyses adjusting for both sex and surgical technique (ß = -0.49 [95% CI, -0.91 to -0.05]; P = .029). There were no cases of reoperation for physeal disturbance in patients who underwent ACLR+LET. Conclusion: The addition of LET to an ACLR with QTA was associated with lower average SIR values and thus improved graft maturity at 2 years postoperatively compared with ACLR alone in skeletally immature patients. The addition of LET to an ACLR was found to be safe in skeletally immature patients.

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