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1.
Circ Res ; 134(7): 875-891, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38440901

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood. METHODS: We applied spatial proteomic approaches to deconvolute the heterogeneity of vascular cells at the single-cell level in situ and characterize cellular alterations of the vascular niches of patients with SSc. Skin biopsies of patients with SSc and control individuals were analyzed by imaging mass cytometry, yielding a total of 90 755 cells including 2987 endothelial cells and 4096 immune cells. RESULTS: We identified 7 different subpopulations of blood vascular endothelial cells (VECs), 2 subpopulations of lymphatic endothelial cells, and 3 subpopulations of pericytes. A novel population of CD34+;αSMA+ (α-smooth muscle actin);CD31+ VECs was more common in SSc, whereas endothelial precursor cells were decreased. Co-detection by indexing and tyramide signal amplification confirmed these findings. The microenvironment of CD34+;αSMA+;CD31+ VECs was enriched for immune cells and myofibroblasts, and CD34+;αSMA+;CD31+ VECs expressed markers of endothelial-to-mesenchymal transition. The density of CD34+;αSMA+;CD31+ VECs was associated with clinical progression of fibrosis in SSc. CONCLUSIONS: Using spatial proteomics, we unraveled the heterogeneity of vascular cells in control individuals and patients with SSc. We identified CD34+;αSMA+;CD31+ VECs as a novel endothelial cell population that is increased in patients with SSc, expresses markers for endothelial-to-mesenchymal transition, and is located in close proximity to immune cells and myofibroblasts. CD34+;αSMA+;CD31+ VEC counts were associated with clinical outcomes of progressive fibrotic remodeling, thus providing a novel cellular correlate for the crosstalk of vasculopathy and fibrosis.


Assuntos
Células Progenitoras Endoteliais , Escleroderma Sistêmico , Humanos , Proteômica , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Fibrose , Miofibroblastos/patologia
2.
Circulation ; 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39342513

RESUMO

BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.

3.
Circulation ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934122

RESUMO

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

4.
FASEB J ; 38(18): e70047, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39292527

RESUMO

Dermal white adipose tissue (DWAT) is a distinctive adipose depot located within the lower dermis of the skin. Its significance as an ancillary fat in skin homoeostasis has recently received increased attention. New research has revealed that DWAT responses to skin pathology and physiology changes, impacting skin development, hair cycling, defense mechanisms, and fibrotic conditions. In this review, we explore the developmental process of DWAT and the adipose commitment timing of hypodermal. We explore the development process of DWAT and its pivotal role in regulating the hair cycle. We conclude the antibacterial activity and reversible dedifferentiation of dermal adipocytes in response to skin defense. Furthermore, we underscore the potentially crucial yet underestimated anti-fibrotic functions of DWAT-derived adipokines and adipocyte-myofibroblast transition.


Assuntos
Tecido Adiposo Branco , Fibrose , Folículo Piloso , Humanos , Tecido Adiposo Branco/metabolismo , Animais , Pele/metabolismo , Pele/patologia , Adipócitos/metabolismo , Derme/patologia , Derme/metabolismo
5.
Arterioscler Thromb Vasc Biol ; 44(4): 915-929, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38357819

RESUMO

BACKGROUND: Until now, the analysis of microvascular networks in the reperfused ischemic brain has been limited due to tissue transparency challenges. METHODS: Using light sheet microscopy, we assessed microvascular network remodeling in the striatum from 3 hours to 56 days post-ischemia in 2 mouse models of transient middle cerebral artery occlusion lasting 20 or 40 minutes, resulting in mild ischemic brain injury or brain infarction, respectively. We also examined the effect of a clinically applicable S1P (sphingosine-1-phosphate) analog, FTY720 (fingolimod), on microvascular network remodeling. RESULTS: Over 56 days, we observed progressive microvascular degeneration in the reperfused striatum, that is, the lesion core, which was followed by robust angiogenesis after mild ischemic injury induced by 20-minute middle cerebral artery occlusion. However, more severe ischemic injury elicited by 40-minute middle cerebral artery occlusion resulted in incomplete microvascular remodeling. In both cases, microvascular networks did not return to their preischemic state but displayed a chronically altered pattern characterized by higher branching point density, shorter branches, higher unconnected branch density, and lower tortuosity, indicating enhanced network connectivity. FTY720 effectively increased microvascular length density, branching point density, and volume density in both models, indicating an angiogenic effect of this drug. CONCLUSIONS: Utilizing light sheet microscopy together with automated image analysis, we characterized microvascular remodeling in the ischemic lesion core in unprecedented detail. This technology will significantly advance our understanding of microvascular restorative processes and pave the way for novel treatment developments in the stroke field.


Assuntos
Isquemia Encefálica , Cloridrato de Fingolimode , Camundongos , Animais , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/uso terapêutico , Infarto da Artéria Cerebral Média/patologia , Microscopia , Encéfalo/irrigação sanguínea , Microvasos/patologia , Modelos Animais de Doenças
6.
Circulation ; 148(3): 268-277, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37459417

RESUMO

More than 16 000 Americans experience spinal cord injury (SCI), resulting in chronic disability and other secondary sequelae, each year. Improvements in acute medical management have increased life expectancy. Cardiovascular disease is a leading cause of death in this population, and seems to occur earlier in individuals with SCI compared with the general population. People with SCI experience a high burden of traditional cardiovascular disease risk factors, including dyslipidemia and diabetes, and demonstrate anatomic, metabolic, and physiologic changes alongside stark reductions in physical activity after injury. They also experience multiple, complex barriers to care relating to disability and, in many cases, compounding effects of intersecting racial and socioeconomic health inequities. Given this combination of risk factors, some investigators have proposed that people with SCI are at increased risk for cardiovascular disease, beyond that associated with traditional risk factors, and SCI could be considered a risk-enhancing factor, analogous to other risk-enhancing factors defined by the 2019 American Heart Association/American College of Cardiology Primary Prevention Guidelines. However, more research is needed in this population to clarify the role of traditional risk factors, novel risk factors, health care access, social determinants of health, and intersectionality of disability, race, and socioeconomic status. There is an urgent need for primary care physicians and cardiologists to have awareness of the importance of timely diagnosis and management of cardiac risk factors for people with SCI.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Traumatismos da Medula Espinal , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/epidemiologia , Fatores de Risco de Doenças Cardíacas
7.
Stroke ; 55(2): 474-483, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38018832

RESUMO

Stroke is a leading cause of paralysis, most frequently affecting the upper limbs and vocal folds. Despite recent advances in care, stroke recovery invariably reaches a plateau, after which there are permanent neurological impairments. Implantable brain-computer interface devices offer the potential to bypass permanent neurological lesions. They function by (1) recording neural activity, (2) decoding the neural signal occurring in response to volitional motor intentions, and (3) generating digital control signals that may be used to control external devices. While brain-computer interface technology has the potential to revolutionize neurological care, clinical translation has been limited. Endovascular arrays present a novel form of minimally invasive brain-computer interface devices that have been deployed in human subjects during early feasibility studies. This article provides an overview of endovascular brain-computer interface devices and critically evaluates the patient with stroke as an implant candidate. Future opportunities are mapped, along with the challenges arising when decoding neural activity following infarction. Limitations arise when considering intracerebral hemorrhage and motor cortex lesions; however, future directions are outlined that aim to address these challenges.


Assuntos
Interfaces Cérebro-Computador , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Paralisia/etiologia , Acidente Vascular Cerebral/complicações , Próteses e Implantes
8.
Clin Infect Dis ; 79(3): 581-582, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325645

RESUMO

Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.


Assuntos
Osteomielite , Úlcera por Pressão , Humanos , Osteomielite/terapia , Úlcera por Pressão/terapia , Pelve/lesões , Qualidade de Vida , Gerenciamento Clínico , Equipe de Assistência ao Paciente
9.
Clin Infect Dis ; 79(3): e11-e26, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325647

RESUMO

Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.


Assuntos
Osteomielite , Úlcera por Pressão , Humanos , Osteomielite/tratamento farmacológico , Úlcera por Pressão/terapia , Pelve/lesões , Gerenciamento Clínico , Qualidade de Vida , Equipe de Assistência ao Paciente
10.
Stroke ; 55(10): 2558-2566, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39212043

RESUMO

Transient ischemic attack (TIA) is traditionally viewed as a self-resolving episode of neurological change without persistent impairments and without evidence of acute brain injury on neuroimaging. However, emerging evidence suggests that TIA may be associated with lingering cognitive dysfunction. Cognitive impairment is a prevalent and disabling sequela of ischemic stroke, but the clinical relevance of this phenomenon after TIA is less commonly recognized. We performed a literature search of observational studies of cognitive function after TIA. There is a consistent body of literature suggesting that rates of cognitive impairment following TIA are higher than healthy controls, but the studies included here are limited by heterogeneity in design and analysis methods. We go on to summarize recent literature on proposed pathophysiological mechanisms underlying the development of cognitive impairment following TIA and finally suggest future directions for further research in this field.


Assuntos
Disfunção Cognitiva , Ataque Isquêmico Transitório , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia
11.
Stroke ; 55(6): 1562-1571, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38716662

RESUMO

BACKGROUND: While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. METHODS: The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. RESULTS: Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th-75th percentile=21.1-30.5). Participants were of median age 54 years (25th-75th percentile=49-59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th-75th percentile=2.2-14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12-1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97-1.40]; ≥2: HR, 1.94 [95% CI, 1.39-2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04-1.64]; National Institutes of Health Stroke Scale score 6-10: HR, 1.64 [95% CI, 1.06-2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18-2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. CONCLUSIONS: In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.


Assuntos
Traumatismos Craniocerebrais , Vida Independente , AVC Isquêmico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , AVC Isquêmico/epidemiologia , Incidência , Fatores de Risco , Adulto , Traumatismos Craniocerebrais/epidemiologia , Estudos Prospectivos , Idoso , Estudos de Coortes
12.
Curr Issues Mol Biol ; 46(1): 327-339, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38248323

RESUMO

Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide's antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists' neuroprotective properties in the context of peripheral nerve injuries.

13.
Am J Epidemiol ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060160

RESUMO

Fall-related injuries (FRIs) are a major cause of hospitalizations among older patients, but identifying them in unstructured clinical notes poses challenges for large-scale research. In this study, we developed and evaluated Natural Language Processing (NLP) models to address this issue. We utilized all available clinical notes from the Mass General Brigham for 2,100 older adults, identifying 154,949 paragraphs of interest through automatic scanning for FRI-related keywords. Two clinical experts directly labeled 5,000 paragraphs to generate benchmark-standard labels, while 3,689 validated patterns were annotated, indirectly labeling 93,157 paragraphs as validated-standard labels. Five NLP models, including vanilla BERT, RoBERTa, Clinical-BERT, Distil-BERT, and SVM, were trained using 2,000 benchmark paragraphs and all validated paragraphs. BERT-based models were trained in three stages: Masked Language Modeling, General Boolean Question Answering (QA), and QA for FRI. For validation, 500 benchmark paragraphs were used, and the remaining 2,500 for testing. Performance metrics (precision, recall, F1 scores, Area Under ROC [AUROC] or Precision-Recall [AUPR] curves) were employed by comparison, with RoBERTa showing the best performance. Precision was 0.90 [0.88-0.91], recall [0.90-0.93], F1 score 0.90 [0.89-0.92], AUROC and AUPR curves of 0.96 [0.95-0.97]. These NLP models accurately identify FRIs from unstructured clinical notes, potentially enhancing clinical notes-based research efficiency.

14.
Am J Epidemiol ; 193(8): 1127-1136, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583944

RESUMO

The rapid expansion of Uber Technologies, Inc.'s ride-sharing, courier service, and food delivery system and e-hailing applications has been transforming the logistics network and urban mobility around the world. We aimed to evaluate the impact of the Uber system on traffic injury (TI) mortality during its implementation in Brazilian capital cities. A quasiexperimental design of interrupted time series was used. The monthly mortality rates for TI standardized by age were analyzed. The date of availability of the Uber app, specific to each capital, was considered the start date. Data from the Brazilian Mortality Information System and the Brazilian Institute of Geography and Statistics were used. For the data analysis, from an interrupted time-series design, autoregressive integrated moving average (ARIMA) models with a transfer function were fitted. In 92.6% (n = 25) of Brazilian capitals, there was no impact of Uber system implementation, 12 months after the start of its activities, on TI mortality. A reduction in mortality from this cause was observed after the system was implemented in Belo Horizonte and Rio de Janeiro. The impact on TI mortality was progressive and continuous in both. More studies are needed to establish the factors associated with the inequalities observed in the impact of Uber system implementation between different locations and the heterogeneity of effects.


Assuntos
Acidentes de Trânsito , Cidades , Análise de Séries Temporais Interrompida , Ferimentos e Lesões , Humanos , Brasil/epidemiologia , Acidentes de Trânsito/mortalidade , Ferimentos e Lesões/mortalidade
15.
Eur J Neurosci ; 60(3): 4201-4216, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38797841

RESUMO

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non-behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat-evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG-ECG resting-state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R-peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non-behavioural determinant of consciousness, we have devised a low-cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non-invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop.


Assuntos
Lesões Encefálicas , Eletroencefalografia , Potenciais Evocados , Frequência Cardíaca , Inconsciência , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Frequência Cardíaca/fisiologia , Eletroencefalografia/métodos , Inconsciência/fisiopatologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/diagnóstico , Potenciais Evocados/fisiologia , Eletrocardiografia/métodos , Estudos Prospectivos , Idoso , Estado Vegetativo Persistente/fisiopatologia , Estado Vegetativo Persistente/diagnóstico , Adulto Jovem
16.
Hum Brain Mapp ; 45(12): e26811, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39185683

RESUMO

Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data. Four datasets were centrally pooled to perform uniform quality control and data preprocessing. A total of 131 non-concussed active athletes (American football, rugby, ice hockey; mean age: 20.06 ± 2.06 years) with baseline and post-season data were included. Nonparametric permutation inference (one-sample t tests, one-sided) was applied to analyze the difference maps of multiple diffusion parameters. The analyses revealed widespread lateralized patterns of sports-season-related increases and decreases in mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across spatially distinct white matter regions. Increases were shown across one MD-cluster (3195 voxels; mean change: 2.34%), one AD-cluster (5740 voxels; mean change: 1.75%), and three RD-clusters (817 total voxels; mean change: 3.11 to 4.70%). Decreases were shown across two MD-clusters (1637 total voxels; mean change: -1.43 to -1.48%), two RD-clusters (1240 total voxels; mean change: -1.92 to -1.93%), and one AD-cluster (724 voxels; mean change: -1.28%). The resulting pattern implies the presence of strain-induced injuries in central and brainstem regions, with comparatively milder physical exercise-induced effects across frontal and superior regions of the left hemisphere, which need further investigation. This article highlights key considerations that need to be addressed in future work to enhance our understanding of the nature of observed white matter changes, improve the comparability of findings across studies, and promote data pooling initiatives to allow more detailed investigations (e.g., exploring sex- and sport-specific effects).


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Substância Branca , Adolescente , Adulto , Humanos , Masculino , Adulto Jovem , Atletas , Traumatismos em Atletas/diagnóstico por imagem , Traumatismos em Atletas/patologia , Traumatismos em Atletas/fisiopatologia , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/patologia , Concussão Encefálica/fisiopatologia , Imagem de Tensor de Difusão , Futebol Americano/lesões , Hóquei/lesões , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
17.
Small ; : e2311128, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888124

RESUMO

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

18.
Small ; : e2405493, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087376

RESUMO

Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.

19.
Histochem Cell Biol ; 161(2): 165-181, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37847258

RESUMO

Burn injuries pose a significant healthcare burden worldwide, often leading to long-term disabilities and reduced quality of life. To explore the impacts of the transplantation of mesenchymal stem cells (MSCs) on the healing of burns and the levels of serum cytokines, 60 fully grown Sprague-Dawley rats were randomly divided into three groups (n = 20 each): group I (control), group II (burn induction), and group III (burn induction + bone marrow (BM)-MSC transplantation). Groups II and III were further divided into four subgroups (n = 5 each) based on euthanasia duration (7, 14, 21, and 28 days post transplant). The experiment concluded with an anesthesia overdose for rat death. After 7, 14, 21, and 28 days, the rats were assessed by clinical, laboratory, and histopathology investigations. The results revealed significant improvements in burn healing potentiality in the group treated with MSC. Furthermore, cytokine levels were measured, with significant increases in interleukin (IL)-6 and interferon alpha (IFN) observed, while IL-10 and transforming growth factor beta (TGF-ß) decreased at 7 days and increased until 28 days post burn. Also, the group that underwent the experiment exhibited increased levels of pro-inflammatory cytokines and the anti-inflammatory cytokine IL-10 when compared to the control group. Histological assessments showed better re-epithelialization, neovascularization, and collagen deposition in the experimental group, suggesting that MSC transplantation in burn wounds may promote burn healing by modulating the immune response and promoting tissue regeneration.


Assuntos
Transplante de Células-Tronco Mesenquimais , Pele , Ratos , Animais , Pele/metabolismo , Interleucina-10/metabolismo , Qualidade de Vida , Ratos Sprague-Dawley , Cicatrização , Citocinas/metabolismo
20.
J Urol ; : 101097JU0000000000004189, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093916

RESUMO

PURPOSE: To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. MATERIALS AND METHODS: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. RESULTS: Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. CONCLUSIONS: In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.

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