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1.
J Neurosurg Pediatr ; : 1-9, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39366023

RESUMO

OBJECTIVE: The objective of this study was to characterize pediatric patients with tight filum terminale (TFT) or fatty filum terminale (FFT) who experienced retethering after transection of the filum, and to determine the risk factors for retethering. METHODS: A systematic review was conducted on May 31, 2023, using PubMed, Google Scholar, SCOPUS, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies detailing retethering following transection for TFT or FFT. Studies were then screened using the Newcastle-Ottawa Scale for risk of bias assessment. RESULTS: Eleven articles met the inclusion criteria with an overall cohort of 1167 patients evaluated for retethering following transection for TFT or FFT. The combined retethering rate across all retrospective studies was 3.4% (95% CI 1.6%-5.2%). A random-effects model was used to estimate the prevalence of presenting symptoms, with the most common being lower-extremity weakness in the overall cohort (54.5%, 95% CI 32.6%-76.4%) and bowel or bladder dysfunction in the retethered cohort (57.9%, 95% CI 41.1%-74.8%). Patients who experienced retethering had a similar estimated prevalence of low-lying conus (71.1%, 95% CI 45.1%-97.1%) compared with the overall cohort (51.1%, 95% CI 39.3%-63.0%). The most common complication following surgery for the overall cohort was a wound complication (2.7%, 95% CI 0.8%-4.6%). Postoperative CSF leakage (OR 13.8, 95% CI 3.9-49.4) was a strong predictor of retethering. Sensory changes at initial presentation were also found to be a predictor of retethering (OR 2.9, 95% CI 1.3-6.5). Low-lying conus was not predictive of retethering. CONCLUSIONS: Preoperative sensory changes and postsurgical CSF leakage were associated with an increased retethering rate following transection of the filum in cases of tethered cord syndrome secondary to fatty filum terminale.

2.
World Neurosurg ; 186: e506-e513, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583560

RESUMO

BACKGROUND: Adult spinal deformity (ASD) significantly impacts the quality of life due to three-dimensional spinal abnormalities. Patient-reported outcome measures, such as the Patient-Reported Outcomes Measurement Information System (PROMIS-29), play a crucial role in assessing postoperative outcomes. This study aims to investigate trends in PROMIS-29 scores over 36 months in patients undergoing long-segment thoracolumbar fusion for ASD and provide insights into its long-term utility. METHODS: A retrospective study including 163 ASD patients undergoing long-segment thoracolumbar fusion was conducted. PROMIS-29 scores were collected at baseline and at postoperative (0-), 3-, 6-, 12-, 18-, 24-, 30-, and 36-month follow-ups. Statistical analyses was performed to assess significant score changes from baseline and in consecutive recordings. RESULTS: Significant improvements in all PROMIS-29 categories were observed at 36 months, with the greatest changes in pain intensity (-35.19%, P < 0.001), physical function (+29.13%, P < 0.001), and pain interference (-28.8%, P < 0.001). Between the 0 and 3 month mark, the greatest significant changes were recorded in pain intensity (-26.5%, P < 0.001), physical function (+24.3%, P < 0.001), and anxiety (-16.9%, P < 0.018). However, scores plateaued after the 3-month mark, with zero categories showing significant changes with subsequent consecutive recordings. CONCLUSIONS: PROMIS-29 scores demonstrated notable improvements in ASD patients particularly in pain intensity, pain interference, and physical function. However, scores plateaued beyond the 3-month mark, suggesting PROMIS-29's limited sensitivity to nuanced changes in long-term patient recovery. Future investigations exploring optimal combinations of patient reported outcome measures for comprehensive short- and long-term outcome assessments in ASD surgery would be beneficial.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Fusão Vertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Fusão Vertebral/métodos , Estudos Retrospectivos , Seguimentos , Adulto , Idoso , Qualidade de Vida , Vértebras Lombares/cirurgia , Resultado do Tratamento , Vértebras Torácicas/cirurgia , Curvaturas da Coluna Vertebral/cirurgia
3.
Biochimie ; 223: 54-73, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38657832

RESUMO

Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for in vitro studies. Using the International Society for Cell & Gene Therapy's criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.


Assuntos
Doenças Autoimunes , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Humanos , Doenças Autoimunes/terapia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Diferenciação Celular , Animais , Transplante de Células-Tronco Mesenquimais , Artrite Reumatoide/terapia , Artrite Reumatoide/patologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo
4.
J Frailty Aging ; 13(1): 40-49, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305442

RESUMO

BACKGROUND: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. OBJECTIVES: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. DESIGN: Cross-sectional analyses within a longitudinal cohort study. SETTING: The multi-center Women's Interagency HIV Study (WIHS). PARTICIPANTS: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47-58 years). MEASUREMENTS: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. RESULTS: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤$12,000 were independently positively associated with frailty; other significant 2005/2006 factors, HIV serostatus, CD4+ count <500 cells/mL among WLWH, smoking, drinking, FIB-4 and eGFR, were not. A newly-derived stepwise model considering all 23 predictors measured in 2018/2019, showed independent positive associations between frailty and age ≥50 years, annual income ≤$12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. CONCLUSION: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH.


Assuntos
Fragilidade , Infecções por HIV , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por HIV/epidemiologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/complicações , Estudos Longitudinais , Qualidade de Vida , Estudos Transversais
5.
AJNR Am J Neuroradiol ; 43(12): 1762-1769, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36357151

RESUMO

BACKGROUND AND PURPOSE: Cognitive improvement has been reported after carotid revascularization and attributed to treating stenosis and correcting hypoperfusion. This study investigated the effect of carotid intraplaque hemorrhage on postintervention cognition. MATERIALS AND METHODS: In this institutional review board-approved single-center study, consecutive patients scheduled for carotid surgery were recruited for preoperative carotid MR imaging (MPRAGE) and pre- and postintervention cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status. Pre- and postintervention scores were compared using t tests and multivariable linear regression. RESULTS: Twenty-three participants were included, with endarterectomy performed in 20 (87%) and angioplasty/stent placement, in 3 (13%). Overall, statistically significant improvements occurred in the pre- versus postintervention mean Total Scale score (92.1 [SD, 15.5] versus 96.1 [SD, 15.8], P = .04), immediate memory index (89.4 [SD, 18.2] versus 97.7 [SD, 14.9], P < .001), and verbal index (96.1 [SD, 14.1] versus 103.0 [SD, 12.0], P = .002). Intraplaque hemorrhage (+) participants (n = 11) had no significant improvement in any category, and the attention index significantly decreased (99.4 [SD, 18.0] versus 93.5 [SD, 19.4], P = .045). Intraplaque hemorrhage (-) participants (n = 12) significantly improved in the Total Scale score (86.4 [SD, 11.8] versus 95.5 [SD, 12.4], P = .004), immediate memory index (82.3 [SD, 14.6] versus 96.2 [SD, 14.1], P = .002), delayed memory index (94.3 [SD, 14.9] versus 102.4 [SD, 8.0], P = .03), and verbal index (94.3 [SD, 13.2] versus 101.5 [SD, 107.4], P = .009). Postintervention minus preintervention scores for intraplaque hemorrhage (+) versus (-) groups showed statistically significant differences in the Total Scale score (-0.4 [SD, 6.8] versus 8.0 [SD, 8.5], P = .02), attention index (-5.9 [SD, 8.5] versus 4.3 [SD, 11.9], P = .03), and immediate memory index (4.2 [SD, 6.7] versus 12.2 [SD, 10.2], P = .04). CONCLUSIONS: Cognitive improvement was observed after carotid intervention, and this was attributable to intraplaque hemorrhage (-) plaque. MR imaging detection of intraplaque hemorrhage status may be an important determinant of cognitive change after intervention.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Hemorragia/terapia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Imageamento por Ressonância Magnética/métodos , Cognição
6.
Cureus ; 14(4): e24008, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35547416

RESUMO

Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.

7.
J Gen Physiol ; 153(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228044

RESUMO

The human voltage-gated proton channel Hv1 is a drug target for cancer, ischemic stroke, and neuroinflammation. It resides on the plasma membrane and endocytic compartments of a variety of cell types, where it mediates outward proton movement and regulates the activity of NOX enzymes. Its voltage-sensing domain (VSD) contains a gated and proton-selective conduction pathway, which can be blocked by aromatic guanidine derivatives such as 2-guanidinobenzimidazole (2GBI). Mutation of Hv1 residue F150 to alanine (F150A) was previously found to increase 2GBI apparent binding affinity more than two orders of magnitude. Here, we explore the contribution of aromatic interactions between the inhibitor and the channel in the presence and absence of the F150A mutation, using a combination of electrophysiological recordings, classic mutagenesis, and site-specific incorporation of fluorinated phenylalanines via nonsense suppression methodology. Our data suggest that the increase in apparent binding affinity is due to a rearrangement of the binding site allowed by the smaller residue at position 150. We used this information to design new arginine mimics with improved affinity for the nonrearranged binding site of the wild-type channel. The new compounds, named "Hv1 Inhibitor Flexibles" (HIFs), consist of two "prongs," an aminoimidazole ring, and an aromatic group connected by extended flexible linkers. Some HIF compounds display inhibitory properties that are superior to those of 2GBI, thus providing a promising scaffold for further development of high-affinity Hv1 inhibitors.


Assuntos
Arginina , Canais Iônicos , Sítios de Ligação , Humanos , Canais Iônicos/metabolismo , Ligantes , Prótons
8.
ACS Sens ; 6(5): 1807-1814, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34010570

RESUMO

Anti-TNF therapeutics bind and sequester tumor necrosis factor (TNF) to prevent downstream signaling and are clinically important in the treatment of several autoimmune diseases. Effective treatment with these drugs requires frequent therapeutic drug monitoring (TDM). Current analytical methods, including reporter gene assay (RGA), enzyme-linked immunosorbent assay (ELISA), and mobility shift assay (MSA), can be technically rigorous, slow, and expensive. These qualities prevent the implementation of point-of-care testing and ultimately limit the frequency and utility of monitoring. An assay simple enough to be performed in the clinic would enable increased TDM frequency, more accurate dosing, and improved patient outcomes. Toward this end, we developed a homogeneous immunoassay based on a tri-part split-luciferase system for "add-and-read" detection of anti-TNF therapeutics. In our platform, two small fragments of the split-luciferase, called ß9 and ß10, are each fused to a different interacting protein. The binding of each of these proteins to anti-TNF antibodies forces the split-luciferase components into proximity where they reform the active luciferase. We identified the fusion proteins, ß9-protein A (ß9-A) and ß10-TNF, as promising binding pairs. We systematically adjusted assay conditions to optimize the signal/background (S/B) ratio, limit of detection (LOD), and percent recovery. The assay has a large dynamic range (0.5-32 µg/mL) and is sensitive enough to monitor both subtherapeutic and supratherapeutic serum concentrations of anti-TNF antibodies, as demonstrated in clinical samples.


Assuntos
Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , Imunoensaio , Infliximab , Luciferases/genética
9.
J Comput Assist Tomogr ; 45(3): 374-382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33797439

RESUMO

ABSTRACT: Ectopic pregnancy (EP) is a known cause of maternal mortality and may be misdiagnosed in up to 50% of pregnant female individuals (Ann Emerg Med. 1996;28(1):10-17). Magnetic resonance imaging, with its superior soft tissue resolution, is a valuable alternative diagnostic modality to diagnose EP when transvaginal ultrasound results are inconclusive. Although an extrauterine gestational sac is the most specific finding, there are other key MRI findings that can aid in diagnosing EP. As availability of MRI access in the emergency department setting increases across the nation, its utility in women with a positive pregnancy test has also increased. Specific MRI findings that are diagnostic of EP include absence of intrauterine pregnancy, adnexal mass separate from the ovary, and hemoperitoneum. In addition, intrauterine ectopic locations, especially intramural, cornual, and cervical pregnancies, can be diagnosed with increased accuracy with the help of MRI. Magnetic resonance imaging is also useful in excluding potential mimics of EP, including adnexal cysts, ovarian neoplasms, and fibroids. In summary, providing an accurate diagnosis and determining the precise location of an EP, which is supported by the use of MRI, is imperative for guiding a patient's treatment to prevent a potentially fatal outcome.


Assuntos
Imageamento por Ressonância Magnética/métodos , Gravidez Ectópica/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Gravidez , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal , Adulto Jovem
10.
Am J Health Behav ; 45(3): 576-587, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33894801

RESUMO

Objectives: Those underage should not use tobacco products, including electronic nicotine delivery systems. A technologically-based solution developed by Juul Labs Inc to restrict underage access seeks to automate transactions, structurally mandate age-verification, and limit the quantity of JUUL products purchased per transaction. A pilot of this standards-based approach, referred to as RACS™ (Retail Access Control Standards), was conducted to assess efficacy. Methods: RACS was implemented at 171 stores within 3 retail chains selling tobacco products in 3 states. "Secret shopper" compliance audits, in which a mystery shopper attempted to purchase JUUL products, were conducted at participating stores before and after implementation of RACS, to test compliance with age-verification and product-quantity limits. Audit failure rates were compared pre- and post-RACS implementation to assess effectiveness. Comparisons were made overall, by chain, state, and failure type. Results: A total of 3990 audits were conducted. We found large, statistically significant reductions (p < .001) in failure rates for age-verification and compliance with product-quantity limits after implementing RACS, as compared to pre-RACS rates, declining to near zero. Conclusions: Utilizing enhanced access controls can be part of a comprehensive, evidence-based tobacco-control strategy to address underage use of all tobacco products, including JUUL.


Assuntos
Comércio , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Comércio/legislação & jurisprudência , Humanos , Projetos Piloto , Produtos do Tabaco/legislação & jurisprudência
11.
J Pharmacol Exp Ther ; 375(2): 296-307, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32958629

RESUMO

Infarct expansion can occur after myocardial infarction (MI), which leads to adverse left ventricular (LV) remodeling and failure. An imbalance between matrix metalloproteinase (MMP) induction and tissue inhibitors of MMPs (TIMPs) can accelerate this process. Past studies have shown different biologic effects of TIMP-3, which may depend upon specific domains within the TIMP-3 molecule. This study tested the hypothesis that differential effects of direct myocardial injections of either a full-length recombinant TIMP-3 (F-TIMP-3) or a truncated form encompassing the N-terminal region (N-TIMP-3) could be identified post-MI. MI was induced in pigs that were randomized for MI injections (30 mg) and received targeted injections within the MI region of F-TIMP-3 (n = 8), N-TIMP-3 (n = 9), or saline injection (MI-only, n = 11). At 14 days post-MI, LV ejection fraction fell post-MI but remained higher in both TIMP-3 groups. Tumor necrosis factor and interleukin-10 mRNA increased by over 10-fold in the MI-only and N-TIMP-3 groups but were reduced with F-TIMP-3 at this post-MI time point. Direct MI injection of either a full-length or truncated form of TIMP-3 is sufficient to favorably alter the course of post-MI remodeling. The functional and differential relevance of TIMP-3 domains has been established in vivo since the TIMP-3 constructs demonstrated different MMP/cytokine expression profiles. These translational studies identify a unique and more specific therapeutic strategy to alter the course of LV remodeling and dysfunction after MI. SIGNIFICANCE STATEMENT: Using different formulations of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), when injected into the myocardial infarction (MI) region, slowed the progression of indices of left ventricular (LV) failure, suggesting that the N terminus of TIMP-3 is sufficient to attenuate early adverse functional events post-MI. Injections of full-length recombinant TIMP-3, but not of the N-terminal region of TIMP-3, reduced relative indices of inflammation at the mRNA level, suggesting that the C-terminal region affects other biological pathways. These unique proof-of-concept studies demonstrate the feasibility of using recombinant small molecules to selectively interrupt adverse LV remodeling post-MI.


Assuntos
Infarto do Miocárdio/patologia , Fragmentos de Peptídeos/farmacologia , Inibidor Tecidual de Metaloproteinase-3/química , Remodelação Ventricular/efeitos dos fármacos , Sequência de Aminoácidos , Colágeno/genética , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções , Metaloproteinases da Matriz/genética , Fragmentos de Peptídeos/química , Domínios Proteicos , RNA Mensageiro/genética , Inibidor Tecidual de Metaloproteinase-3/genética
12.
Proc Natl Acad Sci U S A ; 117(24): 13490-13498, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32461356

RESUMO

The voltage-gated Hv1 proton channel is a ubiquitous membrane protein that has roles in a variety of cellular processes, including proton extrusion, pH regulation, production of reactive oxygen species, proliferation of cancer cells, and increased brain damage during ischemic stroke. A crystal structure of an Hv1 construct in a putative closed state has been reported, and structural models for the channel open state have been proposed, but a complete characterization of the Hv1 conformational dynamics under an applied membrane potential has been elusive. We report structural models of the Hv1 voltage-sensing domain (VSD), both in a hyperpolarized state and a depolarized state resulting from voltage-dependent conformational changes during a 10-µs-timescale atomistic molecular dynamics simulation in an explicit membrane environment. In response to a depolarizing membrane potential, the S4 helix undergoes an outward displacement, leading to changes in the VSD internal salt-bridge network, resulting in a reshaping of the permeation pathway and a significant increase in hydrogen bond connectivity throughout the channel. The total gating charge displacement associated with this transition is consistent with experimental estimates. Molecular docking calculations confirm the proposed mechanism for the inhibitory action of 2-guanidinobenzimidazole (2GBI) derived from electrophysiological measurements and mutagenesis. The depolarized structural model is also consistent with the formation of a metal bridge between residues located in the core of the VSD. Taken together, our results suggest that these structural models are representative of the closed and open states of the Hv1 channel.


Assuntos
Ativação do Canal Iônico , Canais Iônicos/química , Canais Iônicos/metabolismo , Cristalografia por Raios X , Guanidinas/metabolismo , Humanos , Ligação de Hidrogênio , Canais Iônicos/genética , Potenciais da Membrana , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Conformação Proteica , Prótons
13.
Cell Tissue Res ; 370(3): 513-521, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28948356

RESUMO

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1ß (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.


Assuntos
Retardo do Crescimento Fetal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Fumaça/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Trofoblastos/efeitos dos fármacos , Animais , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Chron Respir Dis ; 14(3): 245-255, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28774206

RESUMO

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality. This study explored how patients conceptualize the causes, symptoms, consequences, treatment, and risk for developing COPD. The study consisted of six focus groups: 39 participants who were adults > 40 and current smoker or have COPD symptoms, family history, or exposures. Although many participants had some familiarity with the breathing, lung function, physical, emotional, and social consequences of COPD, confusion and misunderstanding prevailed. Few knew that COPD, chronic bronchitis, and emphysema are synonymous. Some participants claimed that they "only" had bronchitis and/or emphysema and not COPD. Some participants described behavioral adaptations to decrease symptom impact and others expressed strong interest in learning how to increase daily functioning. Insufficient knowledge and persisting misconceptions about COPD can prevent patients from accessing life-enhancing strategies. Patients can benefit from (1) providers clarifying COPD's connection to chronic bronchitis and emphysema to aid them in recognizing the need for mitigating action; (2) encouraging smoking cessation, specifically to stem worsening of disease; and (3) explaining lifestyle adaptations for easing daily life despite decreased lung function.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/psicologia , Atividades Cotidianas , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Abandono do Hábito de Fumar
15.
J Acoust Soc Am ; 141(6): 4209, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28618821

RESUMO

The present study examined the efficacy of 5 MHz low-intensity focused ultrasound (LiFU) as a stimulus to remotely activate inner ear vestibular otolith organs. The otolith organs are the primary sensory apparati responsible for detecting orientation of the head relative to gravity and linear acceleration in three-dimensional space. These organs also respond to loud sounds and vibration of the temporal bone. The oyster toadfish, Opsanus tau, was used to facilitate unobstructed acoustic access to the otolith organs in vivo. Single-unit responses to amplitude-modulated LiFU were recorded in afferent neurons identified as innervating the utricle or the saccule. Neural responses were equivalent to direct mechanical stimulation, and arose from the nonlinear acoustic radiation force acting on the otolithic mass. The magnitude of the acoustic radiation force acting on the otolith was measured ex vivo. Results demonstrate that LiFU stimuli can be tuned to mimic directional forces occurring naturally during physiological movements of the head, loud air conducted sound, or bone conducted vibration.


Assuntos
Mecanotransdução Celular , Neurônios Aferentes/fisiologia , Membrana dos Otólitos/inervação , Ondas Ultrassônicas , Potenciais Evocados Miogênicos Vestibulares , Animais , Batracoidiformes , Feminino , Masculino , Fatores de Tempo
16.
BMC Palliat Care ; 16(1): 33, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28521799

RESUMO

BACKGROUND: The purpose of this study was to compare the differences across occupational groups related to their end-of-life care-specific educational needs and reported intensity of interprofessional collaboration in long-term care (LTC) homes. METHODS: A cross-sectional survey, based on two questionnaires, was administered at four LTC homes in Ontario, Canada using a modified Dilman's approach. The first questionnaire, End of Life Professional Caregiver Survey, included three domains: patients and family-centered communication, cultural and ethical values, effective care delivery. The Intensity of Interprofessional Collaboration Scale included two subscales: care sharing activities, and interprofessional coordination. In total, 697 LTC staff were given surveys, including personal support workers, support staff (housekeeping, kitchen, recreation, laundry, dietician aids, office staff), and registered staff (licensed nurses, physiotherapists, social workers, pharmacists, physicians). RESULTS: A total of 317 participants completed the survey (126 personal support workers, 109 support staff, 82 registered staff) for a response rate of 45%. Significant differences emerged among occupational groups across all scales and subscales. Specifically, support staff rated their comfort of working with dying patients significantly lower than both nurses and PSWs. Support staff also reported significantly lower ratings of care sharing activities and interprofessional coordination compared to both registered staff and personal support workers. CONCLUSIONS: These study findings suggest there are differing educational needs and sense of interprofessional collaboration among LTC staff, specific to discipline group. Both the personal support workers and support staff groups appeared to have higher needs for education; support staff also reported higher needs related to integration on the interdisciplinary team. Efforts to build capacity within support staff related to working with dying residents and their families are needed. Optimal palliative care may require resources to increase the availability of support for all staff involved in the care of patients.


Assuntos
Avaliação das Necessidades , Ocupações , Cuidados Paliativos/métodos , Educação de Pacientes como Assunto/métodos , Adulto , Estudos Transversais , Feminino , Humanos , Relações Interprofissionais , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Ontário , Psicometria/instrumentação , Psicometria/métodos , Inquéritos e Questionários , Recursos Humanos
17.
Med Phys ; 43(11): 6129, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27806609

RESUMO

PURPOSE: Radiography and tomography using proton beams promise benefit to image guidance and treatment planning for proton therapy. A novel proton tracking detector is described and experimental demonstrations at a therapy facility are reported. A new type of proton CT reconstructing relative "scattering power" rather than "stopping power" is also demonstrated. Notably, this new type of imaging does not require the measurement of the residual energies of the protons. METHODS: A large area, silicon microstrip tracker with high spatial and temporal resolution has been developed by the Proton Radiotherapy Verification and Dosimetry Applications consortium and commissioned using beams of protons at iThemba LABS, Medical Radiation Department, South Africa. The tracker comprises twelve planes of silicon developed using technology from high energy physics with each plane having an active area of ∼10 × 10 cm segmented into 2048 microstrips. The tracker is organized into four separate units each containing three detectors at 60° to one another creating an x-u-v coordinate system. Pairs of tracking units are used to reconstruct vertices for protons entering and exiting a phantom containing tissue equivalent inserts. By measuring the position and direction of each proton before and after the phantom, the nonlinear path for each proton through an object can be reconstructed. RESULTS: Experimental results are reported for tracking the path of protons with initial energies of 125 and 191 MeV. A spherical phantom of 75 mm diameter was imaged by positioning it between the entrance and exit detectors of the tracker. Positions and directions of individual protons were used to create angular distributions and 2D fluence maps of the beam. These results were acquired for 36 equally spaced projections spanning 180°, allowing, for the first time, an experimental CT image based upon the relative scattering power of protons to be reconstructed. CONCLUSIONS: Successful tracking of protons through a thick target (phantom) has demonstrated that the tracker discussed in this paper can provide the precise directional information needed to perform proton radiography and tomography. When synchronized with a range telescope, this could enable the reconstruction of proton CT images of stopping power. Furthermore, by measuring the deflection of many protons through a phantom, it was demonstrated that it is possible to reconstruct a new kind of CT image (scattering power) based upon this tracking information alone.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Prótons , Silício , Tomografia Computadorizada por Raios X , Humanos , Radiometria
18.
AJNR Am J Neuroradiol ; 37(8): 1496-503, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27102316

RESUMO

BACKGROUND AND PURPOSE: Carotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage. MATERIALS AND METHODS: This was a retrospective cohort study of 96 patients who underwent carotid MRA and CTA within 1 month, from 2009 to 2016. We excluded occlusions (n = 4) and near occlusions (n = 0), leaving 188 carotid arteries. Intraplaque hemorrhage was detected by using MPRAGE. Calcification, adventitial pattern, stenosis, maximum plaque thickness (total, soft, and hard), ulceration, and intraluminal thrombus on CTA were recorded. Atherosclerosis risk factors and medications were recorded. We used mixed-effects multivariable Poisson regression, accounting for 2 vessels per patient. For the final model, backward elimination was used with a threshold of P < .10. Receiver operating characteristic analysis determined intraplaque hemorrhage by using the area under the curve. RESULTS: Our final model included the rim sign (prevalence ratio = 11.9, P < .001) and maximum soft-plaque thickness (prevalence ratio = 1.2, P = .06). This model had excellent intraplaque hemorrhage prediction (area under the curve = 0.94), outperforming the rim sign, maximum soft-plaque thickness, NASCET stenosis, and ulceration (area under the curve = 0.88, 0.86, 0.77, and 0.63, respectively; P < .001). Addition of the rim sign performed better than each marker alone, including maximum soft-plaque thickness (area under the curve = 0.94 versus 0.86, P < .001), NASCET stenosis (area under the curve = 0.90 versus 0.77, P < .001), and ulceration (area under the curve = 0.90 versus 0.63, P < .001). CONCLUSIONS: The CTA rim sign of adventitial calcification with internal soft plaque is highly predictive of carotid intraplaque hemorrhage.


Assuntos
Calcinose/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Hemorragia , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Área Sob a Curva , Calcinose/patologia , Estenose das Carótidas/patologia , Estudos de Coortes , Feminino , Hemorragia/etiologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Prevalência , Curva ROC , Estudos Retrospectivos , Fatores de Risco
19.
BJR Case Rep ; 1(1): 20150052, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-30363213

RESUMO

A 24-year-old female presented with granulomatous slack skin (GSS) cutaneous T-cell lymphoma. The patient underwent systemic chemotherapy. Owing to the development of several chemotherapy-related complications, therapy was discontinued. Subsequently, disease progression was noted clinically. Our patient's disease progression was clearly demonstrated by 18F-fludeoxyglucose positron emission tomography (PET)/CT findings. PET/CT imaging findings of GSS have not yet previously been reported. In this report, we present PET/CT characteristics of a patient with GSS.

20.
Contemp Clin Trials ; 40: 47-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25460343

RESUMO

BACKGROUND: Home-based rehabilitation following total knee replacement surgery can be as effective as clinic-based or in-patient rehabilitation. The use of the Nintendo Wii has been postulated as a novel rehabilitation tool that adds an additional focus on balance and proprioception into the recovery protocol. The aim of the proposed clinical trial is to investigate the effectiveness of this novel rehabilitation tool, used at home for three months after total knee replacement surgery and to assess any lasting improvements in functional outcome at one year. METHODS/DESIGN: This will be a randomised controlled trial of 128 patients undergoing primary total knee replacement. The participants will be recruited preoperatively from three surgeons at a single centre. There will be no change to the usual care provided until 6 weeks after the operation. Then participants will be randomised to either the Wii-Fit group or usual rehabilitative care group. Outcomes will be assessed preoperatively, a 6-week post surgery baseline and then at 18 weeks, 6 months and 1 year. The primary outcome is the change in self-reported WOMAC total score from week 6 to 18 weeks. Secondary outcomes include objective measures of strength, function and satisfaction scores. DISCUSSION: The results of this clinical trial will be directly relevant for implementation into clinical practice. If beneficial, this affordable technology could be used by many patients to rehabilitate at home. Not only could it optimize the outcomes from their total knee replacement surgery but decrease the need for clinic-based or outpatient therapy for the majority. TRIAL REGISTRATION: (ACTRN12611000291987).


Assuntos
Artroplastia do Joelho/reabilitação , Terapia por Exercício/métodos , Jogos de Vídeo , Feminino , Humanos , Masculino , Satisfação do Paciente , Equilíbrio Postural , Propriocepção , Recuperação de Função Fisiológica , Projetos de Pesquisa
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