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1.
Exp Brain Res ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963558

RESUMO

Bilateral transcutaneous auricular vagus nerve stimulation (taVNS) - a non-invasive neuromodulation technique - has been investigated as a safe and feasible technique to treat many neuropsychiatric conditions. such as epilepsy, depression, anxiety, and chronic pain. Our aim is to investigate the effect of taVNS on neurophysiological processes during emotional and Go/No-Go tasks, and changes in frontal alpha asymmetry. We performed a randomized, double-blind, sham-controlled trial with 44 healthy individuals who were allocated into two groups (the active taVNS group and the sham taVNS group). Subjects received one session of taVNS (active or sham) for 60 min. QEEG was recorded before and after the interventions, and the subjects were assessed while exposed to emotional conditions with sad and happy facial expressions, followed by a Go/No-Go trial. The results demonstrated a significant increase in N2 amplitude in the No-Go condition for the active taVNS post-intervention compared to the sham taVNS after adjusting by handedness, mood, and fatigue levels (p = 0.046), significantly reduced ERD during sad conditions after treatment (p = 0.037), and increased frontal alpha asymmetry towards the right frontal hemisphere during the emotional task condition (p = 0.046). Finally, we observed an interesting neural signature in this study that suggests a bottom-up modulation from brainstem/subcortical to cortical areas as characterized by improved lateralization of alpha oscillations towards the frontal right hemisphere, and changes in ERP during emotional and Go/No-Go tasks that suggests a better subcortical response to the tasks. Such bottom-up effects may mediate some of the clinical effects of taVNS.

2.
Biomed Eng Lett ; 14(4): 677-687, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38946812

RESUMO

Purpose: The purpose of this study was to investigate the neuromodulatory effects of transauricular vagus nerve stimulation (taVNS) and determine optimal taVNS duration to induce the meaningful neuromodulatroty effects using resting-state electroencephalography (EEG). Method: Fifteen participants participated in this study and taVNS was applied to the cymba conchae for a duration of 40 min. Resting-state EEG was measured before and during taVNS application. EEG power spectral density (PSD) and brain network indices (clustering coefficient and path length) were calculated across five frequency bands (delta, theta, alpha, beta and gamma), respectively, to assess the neuromodulatory effect of taVNS. Moreover, we divided the whole brain region into the five regions of interest (frontal, central, left temporal, right temporal, and occipital) to confirm the neuromodulation effect on each specific brain region. Result: Our results demonstrated a significant increase in EEG frequency powers across all five frequency bands during taVNS. Furthermore, significant changes in network indices were observed in the theta and gamma bands compared to the pre-taVNS measurements. These effects were particularly pronounced after approximately 10 min of stimulation, with a more dominant impact observed after approximately 20-30 min of taVNS application. Conclusion: The findings of this study indicate that taVNS can effectively modulate the brain activity, thereby exerting significant effects on brain characteristics. Moreover, taVNS duration of approximately 20-30 min was considered appropriate for inducing a stable and efficient neuromodulatory effects. Consequently, these findings have the potential to contribute to research aimed at enhancing cognitive and motor functions through the modulation of EEG using taVNS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00361-8.

3.
Nanotheranostics ; 8(4): 427-441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38961889

RESUMO

Background: The blood-brain barrier (BBB) is a major bottleneck in delivering therapeutics to the brain. Treatment strategies to transiently open this barrier include focused ultrasound combined with intravenously injected microbubbles (FUS+MB) and targeting of molecules that regulate BBB permeability. Methods: Here, we investigated BBB opening mediated by the claudin-5 binder cCPEm (a microorganismal toxin in a truncated form) and FUS+MB at a centre frequency of 1 MHz, assessing dextran uptake, broadband emission, and endogenous immunoglobulin G (IgG) extravasation. Results: FUS+MB-induced BBB opening was detectable at a pressure ≥0.35 MPa when assessed for leakage of 10 and 70 kDa dextran, and at ≥0.2 MPa for uptake of endogenous IgG. Treating mice with 20 mg/kg cCPEm failed to open the BBB, and pre-treatment with cCPEm followed by FUS+MB at 0.2 and 0.3 MPa did not overtly increase BBB opening compared to FUS+MB alone. Using passive cavitation detection (PCD), we found that broadband emission correlated with the peak negative pressure (PNP) and dextran leakage, indicating the possibility of using broadband emission for developing a feedback controller to monitor BBB opening. Conclusions: Together, our study highlights the challenges in developing combinatorial approaches to open the BBB and presents an additional IgG-based histological detection method for BBB opening.


Assuntos
Barreira Hematoencefálica , Claudina-5 , Microbolhas , Animais , Barreira Hematoencefálica/metabolismo , Camundongos , Claudina-5/metabolismo , Imunoglobulina G/metabolismo , Ondas Ultrassônicas , Camundongos Endogâmicos C57BL , Dextranos/química , Dextranos/farmacocinética
4.
Artigo em Inglês | MEDLINE | ID: mdl-38977483

RESUMO

PURPOSE: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients. STUDY DESIGN: Prospective cohort multicenter study. SETTING: Tertiary referral hospitals. METHODS: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery. RESULTS: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery. CONCLUSION: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus.

5.
J Stroke Cerebrovasc Dis ; : 107857, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38997048

RESUMO

OBJECTIVES: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10-15% of the treatment benefit. We aimed to develop a novel MRI-ADC-based metric that quantify the degree of tissue injury to test the hypothesis that it outperforms infarct volume in predicting long-term outcome. MATERIALS AND METHODS: A single-center cohort consisted of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥2b), and MRI of the brain between 12 hours and 7 days post-EVT. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC <620 threshold. Logistic regression quantified the association of lesion volumes and good outcome (90-day modified Rankin Scale ≤2) at a range of lower ADC thresholds (<570, <520, and <470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between imaging/clinical metrics and functional outcome. RESULTS: 120 patients underwent MRI after successful EVT. Lesion volume based on the ADC threshold <470 had the strongest association with good outcome (OR: 0.81 per 10mL; 95% CI: 0.66-0.99). In a multivariate model, infarct density (<470/<620 * 100) was independently associated with good outcome (aOR 0.68 per 10%; 95% CI: 0.49-0.95), but final infarct volume was not (aOR 0.98 per 10mL; 95% CI: 0.85-1.14). CONCLUSIONS: Infarct density after EVT is more strongly associated with long-term clinical outcome than infarct volume.

6.
Neurointervention ; 19(2): 118-122, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38835141

RESUMO

A patient presented with acute onset headache and subsequent unconsciousness. The neurologic exam showed left-sided myoclonic jerking and right flaccid hemiparalysis. Noncontrast computed tomography revealed diffuse subarachnoid hemorrhage (SAH) with acute hydrocephalus. Initial digital subtraction angiography (DSA) showed no culprit source for SAH. Repeat DSA on day 7 after initial presentation raised suspicion for left internal carotid artery ophthalmic segment and left lateral lenticulostriate artery (LSA) aneurysms. A magnetic resonance vessel wall imaging (VWI) exam was performed given the presence of multiple potential culprit aneurysms. Vessel wall enhancement around the dome of the left LSA aneurysm suggested rupture, which then facilitated treatment with surgical clipping. LSA aneurysms are exceedingly rare and challenging to treat. Given the associated high degree of morbidity, expedient diagnosis is critical to direct management. VWI could be a valuable tool for detecting ruptured aneurysms in the setting of angiogram-negative SAH.

7.
Neuromodulation ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878053

RESUMO

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults. MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation. RESULTS: The participants' age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability. CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

8.
Heliyon ; 10(11): e32156, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38873682

RESUMO

This study conducted in the Kyungpook National University Eco-friendly Agriculture Research Centre between 2022 and 2023 investigates the environmental implications of fence-type solar photovoltaic (PV) systems in diverse agricultural settings. Despite the increasing adoption of solar energy for climate change mitigation, there is a noticeable gap in research regarding the potential environmental impact of these specific PV systems. Focusing on heavy metal concentrations, including Cadmium (Cd), Copper (Cu), Arsenic (As), Mercury (Hg), Lead (Pb), Hexavalent Chromium (Cr+6), Zinc (Zn), and Nickel (Ni), across distinct fields, the study reveals significant fluctuations. Notably, the Rice Field experienced a substantial increase in Cd levels from 0.47 mg/kg in 2022 to 1.55 mg/kg in 2023, while Cu and Pb concentrations decreased to acceptable levels in 2023. The findings underscore the dynamic nature of heavy metal concentrations, emphasizing the importance of continuous soil quality monitoring to prevent contamination. This research provides valuable insights into the impact of fence-type solar PV system installations on agricultural soil quality, emphasizing the urgent need to secure these ecosystems through vigilant monitoring and environmental management practices.

10.
Eur J Radiol ; 177: 111547, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38852329

RESUMO

BACKGROUND: Stroke, a leading global cause of mortality and neurological disability, is often associated with atherosclerotic carotid artery disease. Distinguishing between symptomatic and asymptomatic carotid artery disease is crucial for appropriate treatment decisions. Radiomics, a quantitative image analysis technique, and ML have emerged as promising tools in medical imaging, including neuroradiology. This systematic review and meta-analysis aimed to evaluate the methodological quality of studies employing radiomics for atherosclerotic carotid artery disease analysis and ML algorithms for culprit plaque identification using CT or MRI. MATERIALS AND METHODS: Pubmed, WoS and Scopus databases were searched for relevant studies published from January 2005 to May 2023. RQS assessed methodological quality of studies included in the review. QUADAS-2 assessed the risk of bias. A meta-analysis and three meta regressions were conducted on study performance based on model type, imaging modality and segmentation method. RESULTS: RQS assessed methodological quality, revealing an overall low score and consistent findings with other radiology domains. QUADAS-2 indicated an overall low risk, except for a single study with high bias. The meta-analysis demonstrated that radiomics-based ML models for predicting culprit plaques had a satisfactory performance, with an AUC of 0.85, surpassing clinical models. However, combining radiomics with clinical features yielded the highest AUC of 0.89. Meta-regression analyses confirmed these findings. MRI-based models slightly outperformed CT-based ones, but the difference was not significant. CONCLUSION: In conclusion, radiomics and ML hold promise for assessing carotid plaque vulnerability, aiding in early cerebrovascular event prediction. Combining radiomics with clinical data enhances predictive performance.

11.
MedComm (2020) ; 5(7): e620, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38903536

RESUMO

Type 2 diabetes mellitus (T2DM) and periodontitis (PD) have intricated connections as chronic inflammatory diseases. While the immune response is a key factor that accounts for their association, the underlying mechanisms remain unclear. To gain a deeper understanding of the connection, we conducted research using a multiomics approach. We generated whole genome and methylation profiling array data from the periodontium of PD patients with DM (PDDM) and without DM to confirm genetic and epigenetic changes. Independent bulk and single-cell RNA sequencing data were employed to verify the expression levels of hypo-methylated genes. We observed a gradual rise in C>T base substitutions and hypomethylation in PD and PDDM patients compared with healthy participants. Furthermore, specific genetic and epigenetic alterations were prominently associated with the Fc-gamma receptor-mediated phagocytosis pathway. The upregulation of these genes was confirmed in both the periodontal tissues of PD patients and the pancreatic tissues of T2DM patients. Through single-cell RNA analysis of peripheral blood mononuclear cells, substantial upregulation of Fc-gamma receptors and related genes was particularly identified in monocytes. Our findings suggest that targeting the Fc-gamma signaling pathway in monocytes holds promise as a potential treatment strategy for managing systemic complications associated with diabetes.

12.
Plants (Basel) ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931087

RESUMO

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

13.
Neuroimage ; 297: 120713, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944171

RESUMO

Research indicates that hearing loss significantly contributes to tinnitus, but it alone does not fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches.

14.
Biomol Ther (Seoul) ; 32(4): 403-423, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38898687

RESUMO

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

15.
Arch. cardiol. Méx ; 94(2): 219-239, Apr.-Jun. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1556919

RESUMO

resumen está disponible en el texto completo


Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

16.
J Stroke ; 26(2): 242-251, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38836271

RESUMO

BACKGROUND AND PURPOSE: In young patients (aged 18-60 years) with patent foramen ovale (PFO)-associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. METHODS: Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. RESULTS: Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24-0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21-0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23-0.95; P=0.035). CONCLUSION: Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

17.
Neuroradiol J ; : 19714009241252623, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718167

RESUMO

INTRODUCTION: In the current paper, the "carotid artery calcium score" method is presented with the target to offer a metric method to quantify the amount of calcification in the carotid artery. MODEL AND DEFINITION: The Volume of Interest (VOI) should be extracted and those voxels, with a Hounsfield Unit (HU) value ≥130, should be considered. The total weight value is determined by calculating the sum of the HU attenuation values of all voxels with values ≥130 HU. This value should be multiplied by the conversion factor ("or voxel size") and divided by a weighting factor, the attenuation threshold to consider a voxel as calcified (and therefore 130 HU): this equation determines the Carotid Artery Calcium Score (CACS). RESULTS: In order to provide the demonstration of the potential feasibility of the model, the CACS was calculated in 131 subjects (94 males; mean age 72.7 years) for 235 carotid arteries (in 27 subjects, unilateral plaque was present) considered. The CACS value ranged from 0.67 to 11716. A statistically significant correlation was found (rho value = 0.663, p value = .0001) between the CACS in the right and left carotid plaques. Moreover, a statistically significant correlation between the age and the total CACS was present (rho value = 0.244, p value = .005), whereas no statistically significant difference was found in the distribution of CACS by gender (p = .148). The CACS was also tested at baseline and after contrast and no statistically significant difference was found. CONCLUSION: In conclusion, this method is of easy application, and it weights at the same time the volume and the degree of calcification in a unique parameter. This method needs to be tested to verify its potential utility, similar to the coronary artery calcium score, for the risk stratification of the occurrence of cerebrovascular events of the anterior circulation. Further studies using this new diagnostic tool to determine the prognostic value of carotid calcium quantification are needed.

18.
Mol Ther Nucleic Acids ; 35(2): 102199, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38766525

RESUMO

Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease with paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research on precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an EYA1 inversion with a deletion, implicated in branchio-oto-renal/branchio-oto syndrome. To address this, two CRISPR-based approaches were tested. First, we used Cas9 nuclease and paired gRNAs tailored to the patient's genome. The dual CRISPR-Cas9 system induced efficient correction of paracentric inversion in patient-derived fibroblast, and effectively restored the expression of EYA1 mRNA and protein, along with its transcriptional activity required to regulate the target gene expression. Additionally, we used CRISPR activation (CRISPRa), which leads to the upregulation of EYA1 mRNA expression in patient-derived fibroblasts. Moreover, CRISPRa significantly improved EYA1 protein expression and transcriptional activity essential for target gene expression. This suggests that CRISPRa-based gene therapies could offer substantial translational potential for approximately 70% of disease-causing EYA1 variants responsible for haploinsufficiency. Our findings demonstrate the potential of CRISPR-guided genome editing for correcting SVs, including those with EYA1 CGR linked to haploinsufficiency.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38719137

RESUMO

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

20.
Int J Biol Macromol ; 271(Pt 1): 132564, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782324

RESUMO

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.


Assuntos
Tendão do Calcâneo , Colágeno , Suturas , Cicatrização , Animais , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/lesões , Ratos , Cicatrização/efeitos dos fármacos , Colágeno/química , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Implantes Absorvíveis , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Regeneração/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia
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