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1.
Pathobiology ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830348

RESUMO

INTRODUCTION: The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. METHODS: We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. RESULTS: Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. CONCLUSION: These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38801238

RESUMO

OBJECTIVE: To investigate the associations between time interval from myomectomy to pregnancy (TIMP) and subsequent pregnancy and obstetric complications, and to explore whether these associations vary according to maternal age at birth. METHODS: A retrospective population-based cohort study was conducted from 2008 to 2017. Data were extracted from the National Health Insurance Research Database and the Taiwan Maternal and Child Health Database, comprising 2024 379 births from 1 391 856 pregnancies. Eligible cases were identified using diagnostic and procedure codes; 4006 first singleton births in 4006 women after their first laparotomic myomectomy were identified. We estimated the risks of pregnancy and obstetric outcomes according to TIMP (<6, 6-11, and ≥12 months). Subgroup analysis was performed by further dividing according to maternal age at birth (18-34 vs ≥35 years old). RESULTS: We observed higher risks of gestational hypertensive disorders (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.22-3.18, P = 0.005) and neonatal death (aOR 4.59, 95% CI 1.49-14.18, P = 0.008) for TIMP of <6 months versus TIMP of 6-11 months. Likewise, a TIMP ≥12 months was associated with increased risks of gestational hypertensive disorders (aOR 1.72, 95% CI 1.14-2.58, P = 0.010), and neonatal death (aOR 3.27, 95% CI 1.16-9.24, P = 0.025) versus a TIMP of 6-11 months. In subgroup analysis, women over 35 years old still had higher risks of gestational hypertensive disorders when TIMP was <6 months (aOR 2.26, 95% CI 1.17-4.37, P = 0.015) or ≥12 months (aOR 2.04, 95% CI 1.17-3.54, P = 0.012), and a higher risk of neonatal death when TIMP was <6 months (aOR 4.05, 95% CI 1.06-15.53, P = 0.041); whereas women aged 18-34 years old did not. CONCLUSIONS: This study suggests that a TIMP between 6 and 11 months is associated with lower risks of gestational hypertensive disorders and neonatal death compared with a TIMP <6 months or ≥12 months, especially for women over 35 years old.

3.
Nurs Health Sci ; 26(2): e13119, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626947

RESUMO

Nurses in neurological wards face numerous challenges when caring for patients with dementia, particularly those who also present other acute illnesses. However, studies focusing on this area are limited. This study aimed to explore the difficulties and strategies in caring for patients with dementia among nurses working in a neurological ward. A qualitative descriptive design was adopted. Twelve nurses from a neurology ward participated in individual semi-structured interviews. The data collected through these interviews were subjected to qualitative content analysis. Two main themes emerged from the analysis: (i) various shortcomings and concerns, which include subthemes: insufficient support, worry about patient safety, inadequate care ability of the caregiver, and insufficient self-competence, and (ii) unique clinical strategies, which include subthemes: cooperate with the caregiver, improve self-competence in dementia care, and employ meticulous resorts. The findings highlighted the nurses' dedication to minimizing patient risks and utilizing available resources as well as stakeholders to provide optimal care. To enhance patient care quality, it is essential to support nurses by addressing care-related barriers, offering continuous education, and establishing care pathways.


Assuntos
Demência , Enfermeiras e Enfermeiros , Humanos , Pesquisa Qualitativa , Hospitais , Educação Continuada , Demência/complicações , Demência/terapia
4.
Am J Bot ; : e16319, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38641926

RESUMO

PREMISE: Endophytic and mycorrhizal fungi are crucial in facilitating plant nutrition acquisition and stress tolerance. In epiphytic habitats, plants face nutrition and water stress, but their roots are mostly nonmycorrhizal and especially lacking in arbuscular mycorrhizal associations. Ophioderma pendulum is an epiphytic fern with a partially mycoheterotrophic lifestyle, likely heavily reliant on symbiotic fungi. To characterize fungal associations in the sporophyte of O. pendulum, we focused on leaves and roots of O. pendulum, seeking to reveal the fungal communities in these organs. METHODS: Roots and leaves from O. pendulum in a subtropical forest were examined microscopically to observe the morphology of fungal structures and determine the percentage of various fungal structures in host tissues. Fungal composition was profiled using metabarcoding techniques that targeted ITS2 of the nuclear ribosomal DNA. RESULTS: Roots were consistently colonized by arbuscular mycorrhizal fungi (Glomeromycota), especially Acaulospora. Unlike previous findings on epiphytic ferns, dark septate endophytes were rare in O. pendulum roots. Leaves were predominantly colonized by Ascomycota fungi, specifically the classes Dothideomycetes (46.88%), Eurotiomycetes (11.51%), Sordariomycetes (6.23%), and Leotiomycetes (6.14%). Across sampling sites, fungal community compositions were similar in the roots but differed significantly in the leaves. CONCLUSIONS: Ophioderma pendulum maintains stable, single-taxon-dominant communities in the roots, primarily featuring arbuscular mycorrhizal fungi, whereas the leaves may harbor opportunistic fungal colonizers. Our study underlines the significance of mycorrhizal fungi in the adaptation of epiphytic ferns.

6.
Int J Biol Macromol ; 269(Pt 2): 131720, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677692

RESUMO

The human nervous system is an incredibly intricate physiological network, and neural cells lack the ability to repair and regenerate after a brain injury. 3-dimensional (3D) bioprinting technology offers a promising strategy for constructing biomimetic organ constructs and in vitro brain/disease models. The bioink serves as a pivotal component that emulates the microenvironment of biomimetic construct and exerts a profound influence on cellular behaviors. In this study, a series of mechanically adjustable and dual crosslinking bioinks were developed using photocrosslinkable methacrylated silk fibroin (SilMA) in combination with the ionic crosslinking material, pectin, or pectin methacryloyl (PecMA) with silk fibroin (SF) supplementation. SilMA/pectin exhibited superior properties, with SilMA providing biocompatibility and adjustable mechanical properties, while the addition of pectin enhanced printability. The porous structure supported neural cell growth, and 15 % SilMA/0.5 % pectin bioinks displayed excellent printability and shape fidelity. Neural stem/progenitor cells (NSPCs)-loaded bioinks were used to construct a 3D brain model, demonstrating sustained vitality and high neuronal differentiation without the need for growth factors. The SilMA/pectin bioinks demonstrated adjustable mechanical properties, favorable biocompatibility, and an environment highly conducive to neural induction, offering an alternative approach for neural tissue engineering applications or in vitro brain models.


Assuntos
Bioimpressão , Fibroínas , Células-Tronco Neurais , Pectinas , Impressão Tridimensional , Esferoides Celulares , Pectinas/química , Fibroínas/química , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Bioimpressão/métodos , Esferoides Celulares/citologia , Alicerces Teciduais/química , Animais , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Diferenciação Celular/efeitos dos fármacos , Tinta
7.
J Formos Med Assoc ; 123(7): 744-750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38485554

RESUMO

BACKGROUND: We evaluated the outcomes of pregnancy in women with congenital heart disease (CHD) and their offspring in Taiwan. We also investigated how different severity levels may influence the outcomes. METHODS: We used data (2009-2017) from the Birth Certificate Application database in Taiwan, which is linked to the National Health Insurance Research Database and Taiwan Maternal and Child Health Database. We identified 2990 women with CHD who had 4227 births. Based on the CHD subtypes, patients were further divided into "severe CHD" and "simple CHD" groups. RESULTS: Women with CHD have a significant risk of stillbirth. In maternal cardiac events, they had the highest risk of heart failure, followed by arrhythmia. The severity of CHD had a significant effect on the outcomes as well. The neonatal birth event that mothers with CHD have the highest risk of is preterm birth at < 32 weeks of gestation. The prominent difference in neonatal morbidities between mothers with severe and simple CHD is recurrent CHD in the offspring. The offspring of the severe CHD group had a higher risk of severe CHD, whereas those of the simple CHD group had a higher risk of simple CHD. CONCLUSION: During pregnancy, the monitoring of heart function and cardiac rhythm could be more intensive in mothers with CHD. In addition to accurately assessing fetal growth and development during antenatal care, mothers with severe CHD should be provided with careful fetal heart structure assessment and genetic testing along with counseling.


Assuntos
Cardiopatias Congênitas , Resultado da Gravidez , Humanos , Feminino , Taiwan/epidemiologia , Gravidez , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/complicações , Recém-Nascido , Adulto , Resultado da Gravidez/epidemiologia , Bases de Dados Factuais , Natimorto/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto Jovem , Complicações Cardiovasculares na Gravidez/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Cuidado Pré-Natal , Idade Gestacional , Modelos Logísticos
8.
Eye (Lond) ; 38(10): 1926-1932, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38548946

RESUMO

OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.


Assuntos
Antirreumáticos , Sequenciamento do Exoma , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hidroxicloroquina , Doenças Retinianas , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Retinianas/genética , Doenças Retinianas/induzido quimicamente , Antirreumáticos/efeitos adversos , Idoso , Adulto , Acuidade Visual , Polimorfismo de Nucleotídeo Único
9.
Heliyon ; 10(6): e28094, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38532994

RESUMO

Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects. Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis. Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups. Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.

11.
Cancers (Basel) ; 16(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38254744

RESUMO

Sonodynamic therapy (SDT) is a novel tumor treatment that combines biosafe sonosensitizers and noninvasive focused ultrasound to eradicate solid tumors. Sonosensitizers such as 5-aminolevulinic acid and fluorescein have great potential in tumor treatment. Here, rodent subcutaneous and brain tumor models were used to evaluate the treatment effect of both 5-ALA- and fluorescein-mediated SDT. The subcutaneous tumor growth rates of both SDT groups were significantly inhibited compared with that of the control groups. For intracranial tumors, 5-ALA-SDT treatment significantly inhibited brain tumor growth, while fluorescein-SDT exerted no therapeutic effect in animals. The distribution of fluorescein in the brain tumor region underwent further assessment. Seven days post tumor implantation, experimental animals received fluorescein and were sacrificed for brain specimen collection. Analysis of the dissected brains revealed no fluorescence signals, indicating an absence of fluorescein accumulation in the early-stage glioma tissue. These data suggest that the fluorescein-SDT treatment response is closely related to the amount of accumulated fluorescein. This study reports the equivalent effects of 5-ALA and fluorescein on the treatment of somatic tumors. For orthotopic brain tumor models, tumor vascular permeability should be considered when choosing fluorescein as a sonosensitizer. In conclusion, both fluorescein and 5-ALA are safe and effective SDT sonosensitizers, and the tumor microenvironment and pathologic type should be considered in the selection of adequate sonosensitizers.

12.
J Dermatol ; 51(2): 150-159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37955334

RESUMO

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes.


Assuntos
Agamaglobulinemia , Febre Familiar do Mediterrâneo , Livedo Reticular , Síndromes Mielodisplásicas , Poliarterite Nodosa , Imunodeficiência Combinada Severa , Dermatopatias Genéticas , Dermatopatias , Vasculite , Adulto , Humanos , Criança , Pessoa de Meia-Idade , Adenosina Desaminase/genética , Livedo Reticular/complicações , Peptídeos e Proteínas de Sinalização Intercelular , Vasculite/diagnóstico , Vasculite/etiologia , Poliarterite Nodosa/complicações , Poliarterite Nodosa/diagnóstico , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Febre Familiar do Mediterrâneo/diagnóstico , Mutação
13.
Int J Gynaecol Obstet ; 164(2): 605-612, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37723982

RESUMO

OBJECTIVE: To investigate the impact of repeated dilatation and curettage or hysteroscopic biopsy on fetomaternal outcomes in patients receiving progestin treatment for endometrial hyperplasia or early-stage carcinoma. METHOD: This was a population-based study using the Taiwan National Health Insurance Research Database between 2009 and 2017 of women who gave birth and had a history of endometrial hyperplasia and early-stage carcinoma treated with progestins. Logistic regression analysis was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) reflecting the association between repeated procedures and fetomaternal outcomes. RESULTS: A total of 6956 women with 8690 deliveries were identified. Compared with those who had two or fewer procedures, women who received more than two procedures had a significantly higher risk for cervical insufficiency (aOR, 5.09 [95 CI, 2.31-11.24]). Furthermore, women who had more than two procedures were prone to have adverse neonatal outcomes, including Apgar score < 7 at 1 min (aOR, 1.97 [95% CI, 1.13-3.43]) and 5 min (aOR, 3.11 [95% CI, 1.33-7.23]) and preterm delivery <32 weeks (aOR, 2.86 [95% CI, 1.50-5.45]). CONCLUSION: Undergoing more than two procedures was associated with subsequent maternal cervical insufficiency, preterm delivery <32 weeks, and low neonatal Apgar score. Health care providers should be aware of the potential risks and balance the benefits and harms of repeated procedures.


Assuntos
Carcinoma , Hiperplasia Endometrial , Neoplasias do Endométrio , Nascimento Prematuro , Recém-Nascido , Humanos , Feminino , Progestinas , Hiperplasia Endometrial/patologia , Nascimento Prematuro/epidemiologia , Taiwan , Dilatação e Curetagem , Biópsia , Neoplasias do Endométrio/patologia
14.
J Clin Neurosci ; 119: 93-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992420

RESUMO

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.


Assuntos
Hemorragia dos Gânglios da Base , Neuroendoscopia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Neuroendoscopia/métodos , Hemorragia dos Gânglios da Base/diagnóstico por imagem , Hemorragia dos Gânglios da Base/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Hematoma/cirurgia
15.
Artigo em Inglês | MEDLINE | ID: mdl-38082691

RESUMO

Digital subtraction angiography (DSA) is a X-ray based imaging modality for interventional procedures, and remains criterion standard for diagnosing vascular diseases. The imaging protocol of DSA involves administration of a foreign contrast medium into the blood vessel that opacifies the vasculature during the imaging. Using two-dimensional (2D) DSA with high temporal resolution, it was recently demonstrated that the pulsatile velocity can be estimated by evaluating the temporal and spatial variations of the contrast medium distributions in the blood vessel. In this paper, we evaluate the feasibility to estimate the pulsatile flow velocity using the four-dimensional (4D) DSA. To overcome the noise and artefacts of 4D-DSA data, a empirical mode decomposition plus autocorrelation based method is proposed to estimate the pulsatile velocities, and the pulsatile velocities estimated using 2D-DSA are used as reference for comparison.Clinical Relevance-4D-DSA encompasses both structural and temporal information; it theoretically reduces the need of multiple scans, hence reducing the radiation doses. The estimated pulsatile flow velocities open up a new parameter for hemodynamic studies and potential for real-time diagnostic and therapeutic monitoring during interventional procedures.


Assuntos
Hemodinâmica , Imageamento Tridimensional , Angiografia Digital/métodos , Fluxo Pulsátil , Imageamento Tridimensional/métodos , Meios de Contraste
16.
J Neurooncol ; 165(3): 535-545, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38060066

RESUMO

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.


Assuntos
Neoplasias Encefálicas , Glioma , Camundongos , Animais , Humanos , Estudos Prospectivos , Projetos Piloto , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Barreira Hematoencefálica/metabolismo , Glioma/diagnóstico por imagem , Glioma/radioterapia , Microambiente Tumoral
17.
J Neurooncol ; 165(2): 361-372, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37917280

RESUMO

PURPOSE: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown. METHODS: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles. RESULTS: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate. CONCLUSION: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate.


Assuntos
Anestesia , Anestésicos , Neoplasias Encefálicas , Glioma , Propofol , Humanos , Adulto , Estudos Retrospectivos , Vigília , Sonolência , Glioma/cirurgia , Glioma/patologia , Craniotomia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia
18.
Brain Sci ; 13(10)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37891740

RESUMO

Astasia refers to the inability to maintain upright posture during standing, despite having full motor strength. Impairment of the vestibulocerebellar pathway, graviceptive system, and cingulate motor area have been proposed to be related to astasia. However, the responsible neural pathways remain unclear. We hypothesize that there is a common neural network behind astasia. To test the hypothesis, we reviewed all reported cases with astasia, including ours, and focused on the correlation between anatomical destruction and symptom presentation. A total of 26, including ours, non-psychogenic astasia patients were identified in the English literature. Seventy-three percent of them were associated with other neurologic symptoms and sixty-two percent of reported lesions were on the right side. Contralateral lateropulsion was very common, followed by retropulsion, when describing astasia. Infarction (54%) was the most reported cause. The thalamus (65%) was the most reported location. Infarctions were the fastest to recover (mean: 10.6 days), while lesions at the brainstem needed a longer time (mean: 61.6 days). By combining the character of lateropulsion in astasia and the presentation of an interrupted graviceptive system, we concluded that the primary graviceptive system may be the common neural network behind astasia. Future studies on astasia should focus on the pathological changes in the perception of verticality in the visual world and the body.

19.
Phys Rev Lett ; 131(13): 133001, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37832013

RESUMO

Dark-state polaritons (DSPs) based on the effect of electromagnetically induced transparency are bosonic quasiparticles, representing the superpositions of photons and atomic ground-state coherences. It has been proposed that stationary DSPs are governed by the equation of motion closely similar to the Schrödinger equation and can be employed to achieve Bose-Einstein condensation (BEC) with transition temperature orders of magnitude higher than that of the atomic BEC. The stationary-DSP BEC is a three-dimensional system and has a far longer lifetime than the exciton-polariton BEC. In this Letter, we experimentally demonstrated the stationary DSP dressed by the Rydberg-state dipole-dipole interaction (DDI). The DDI-induced phase shift of the stationary DSP was systematically studied. Notably, the experimental data are consistent with the theoretical predictions. The phase shift can be viewed as a consequence of elastic collisions. In terms of thermalization to achieve BEC, the µm^{2}-size interaction cross section of the DDI can produce a sufficient elastic collision rate for the stationary DSPs. This Letter makes a substantial advancement toward the realization of the stationary-DSP BEC.

20.
J Neurooncol ; 164(2): 483-491, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37668943

RESUMO

PURPOSE: Neuroplasticity is an ability to maintain neural circuit function when facing damages. It is one of the reasons that making brain tumors notorious. Therefore, we evaluated the characteristics of patients with primary brain tumors, compared neuropsychological deficits between patients who had awake craniotomy with left- or right-sided tumors, and analyzed the association between white matter tracts and neuropsychological deficits in patients with right-sided tumors. METHODS: Using the registration dataset of Chang Gung Memory Hospital between 2014 and 2020, this study included a total of 698 adult patients who received craniotomy for primary brain tumors (538 of conventional craniotomy; 160 of awake craniotomy). Neuropsychological assessments were arranged in patients as preoperative evaluation for awake craniotomies. RESULTS: A lower proportion of right-sided tumors was noted in patient who had awake craniotomy than those who had conventional craniotomy (33.8% and 51.5%, p < 0.001). In awake craniotomy, 88.7% of patients with left-sided tumors and 77.8% of patients with right-sided tumors had neuropsychological impairment. Patients with left-sided tumors had worse preoperative performance compared to those with right-sided tumors in global function (36.2% and 8.0%, p < 0.001), language domain (57.6% and 22.2%, p < 0.001), and attention (36.0% and 18.5%, p = 0.02). Furthermore, in those with right-sided low-grade gliomas, patients involving pathway of superior longitudinal fasciculus (SLF) I had a higher risk of deficits than those without involvement in verbal memory (p = 0.001, Odd ratio = 11.2, 95% CI = 1.8 ~ 71.4) and visual memory (p = 0.048, Odd ratio = 10.5, 95% CI = 1.0 ~ 111). CONCLUSION: In awake craniotomy, patients with left-sided brain tumors had worse cognitive function than those with right-sided tumors in terms of global function, language, and attention. 77% of patients with right-sided tumors had neuropsychological impairment. Therefore, a comprehensive neuropsychological evaluation and awake craniotomy are necessary for patients with brain tumors.

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