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Τετάρτη 11 Νοεμβρίου 2020

[ASAP] Microenvironment-Triggered Degradable Hydrogel for Imaging Diagnosis and Combined Treatment of Intraocular Choroidal Melanoma

Alexandros G.Sfakianakis shared this article with you from Inoreader

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ACS Nano
DOI: 10.1021/acsnano.0c06000
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Flow‐diverting stents in the treatment of peripheral and visceral artery aneurysms

Alexandros G.Sfakianakis shared this article with you from Inoreader

Abstract

Objective

This meta‐analysis aims to evaluate the safety and efficacy of flow‐diverting stents (FDS) in treating peripheral and visceral artery aneurysms (PAA/VAAs).

Background

Though rare, PAA/VAAs can represent a life‐threatening condition due to their propensity of rupture. The FDS emerges as a new solution to exclude these aneurysms while maintaining collateral branches, but convincing evidence is lacking on its clinical effectiveness.

Methods

A systematic literature search was performed to identify studies related to FDS in treating PAA/VAAs. The preferred reporting items for systematic reviews and meta‐analyses (PRISMA) statement was applied to guide the data extraction, quality assessment, and synthesis of outcomes of interest. Random effect models were applied to calculate the event rates of major endpoints. OpenMeta[Analyst] software was used for statistical analysis.

Results

Of 130 records screened, 10 cohort studies (including 220 patients, average age: 66.0 years, 78.4% male) were enrolled in the meta‐analysis. Pooled data suggested a technical success rate of 98.5% (95% CI: 97.0–100%). During a mean follow‐up period of 14.1 months, 93.6% (95% CI: 88.6–98.5%) side branches remained patent, 89.8% (95% CI: 84.3–95.3%) aneurysms were totally thrombosed, whereas shrinkage/stabilization of the aneurysm was documented in 93.4% (95% CI: 88.4–98.4%) cases. The primary stent patency rate was estimated to be 87.9% (95% CI: 81.0–94.8%). Overall clinical success was achieved in 83.2% (95% CI: 74.4–92.0%) patients.

Conclusions

The FDS features a potential advantage of preserving side branches while inducing sac thrombosis and aneurysm shrinkage/stabilization. Further prospective, comparative studies in larger patient cohorts are anticipated to draw a robust conclusion.

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Usefulness of updated logistic clinical SYNTAX score based on MI‐SYNTAX score in patients with ST‐elevation myocardial infarction

Alexandros G.Sfakianakis shared this article with you from Inoreader

Abstract

Objectives

To compare the predictive performances of the prewiring, postwiring MI‐SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2‐year all‐cause mortality post percutaneous coronary intervention (PCI) in ST‐elevation myocardial infarction (STEMI) patients.

Background

In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI‐SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long‐term all‐cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors.

Methods

In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities.

Results

Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high‐score groups were associated with higher rates of 2‐year all‐cause mortality compared to the low‐score groups (6.6 vs. 1.2%; log‐rank p = .001 and 6.6 vs. 1.2%; log‐rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI‐SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI‐SYNTAX score had a better discrimination for the mortality than the postwiring MI‐SYNTAX score (IDI ‐0.0082; p = .029). The four scores had acceptable calibration abilities for 2‐year all‐cause mortality.

Conclusions

The prewiring Updated LCSS predicts long‐term all‐cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI‐SYNTAX score does not improve mortality prediction, the prewiring MI‐SYNTAX score may be preferred for the 2‐year mortality prediction using the Updated LCSS.

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TDP-43 proteinopathies: a new wave of neurodegenerative diseases

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclu sions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding (TARDBP) and unrelated genes (eg, C9orf72). While TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, determining the pathophysiological mechanisms through which TDP-43 mediates neurodegeneration appears complex, and unravelling these molecular processes seems critical for the development of effective therapies. This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration.

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Kinetic Modelling and Test–Retest Reproducibility for the Dopamine D 1 R Radioligand [ 11 C]SCH23390 in Healthy and Diseased Mice

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Abstract

Purpose

Our aim in this study was to compare different non-invasive pharmacokinetic models and assess test–retest reproducibility of the radioligand [11C]SCH23390 for the quantification of dopamine D1-like receptor (D1R) in both wild-type (WT) mice and heterozygous (HET) Q175DN mice as Huntington's disease (HD) model.

Procedures

Adult WT (n = 9) and HET (n = 14) mice underwent a 90-min [11C]SCH23390 positron emission tomography (PET) scan followed by computed tomography (CT) to evaluate the pharmacokinetic modelling in healthy and diseased conditions. Additionally, 5 WT mice and 7 HET animals received a second [11C]SCH23390 PET scan for test–retest reproducibility. Parallel assessment of the simplified reference tissue model (SRTM), the multilinear reference tissue model (MRTM) and the Logan reference tissue model (Logan Ref) using the striatum as a receptor-rich region and the cerebellum as a receptor-free (reference) region was performed to define the most suitable method for regional- and voxel-based quantification of the binding potential (BPND). Finally, standardised uptake value ratio (SUVR-1) was assessed as a potential simplified measurement.

Results

For all models, we measured a significant decline in dopamine D1R density (e.g. SRTM = − 38.5 ± 5.0 %, p < 0.0001) in HET mice compared to WT littermates. Shortening the 90-min scan duration resulted in large underestimation of striatal BPND in both WT mice (SRTM 60 min: − 17.7 ± 2.8 %, p = 0.0078) and diseased HET (SRTM 60 min: − 13.1 ± 4.1 %, p = 0.0001). Striatal BPND measurements were very reproducible with an average test–retest variability below 5 % when using both MRTM and SRTM. Parametric BPND maps generated with SRTM were highly reliable, showing nearly perfect agreement to the regional analysis (r2 = 0.99, p < 0.0001). Finally, SRTM provided the most accurate estimate for relative tracer delivery R1 with both r egional- and voxel-based analyses. SUVR-1 at different time intervals were not sufficiently reliable when compared to BPND (r2 < 0.66).

Conclusions

Ninety-minute acquisition and the use of SRTM for pharmacokinetic modelling is recommended. [11C]SCH23390 PET imaging demonstrates optimal characteristics for the study of dopamine D1R density in models of psychiatric and neurological disorders as exemplified in the Q175DN mouse model of HD.

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Aberrant ALOX5 Activation Correlates with HER2 Status and Mediates Breast Cancer Biological Activities through Multiple Mechanisms

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Arachidonate lipoxygenases (ALOX) have been implicated in playing a critical role in tumorigenesis, development, and metastasis. We previously reported that ALOX12 is involved in breast cancer chemoresistance. In this study, we demonstrate that the ALOX5 activation correlates with the HER2 expression and mediates breast cancer growth and migration. We found that the ALOX5 expression and activity were upregulated in breast cancer patients, particularly in those tissues with HER2-positive. ALOX5 upregulation was also observed in HER2-positive breast cancer cells. In contrast, HER2 inhibition led to decreased expression and activity of ALOX5 but not ALOX5AP, suggesting that HER2 specifically regulates the ALOX5 expression and activity in breast cancer cells. We further demonstrated that ALOX5 is important for breast cancer biological activities with the predominant roles in growth and migration, likely through RhoA, focal adhesion, and PI3K/Akt/mTOR signaling but not epithelial mesenchymal transition (EMT). Our work is the first to report a correlation between the ALOX5 activity and HER2 overexpression in breast cancer. Our findings also highlight the therapeutic value of inhibiting ALOX5 in breast cancer, particularly those patients with the HER2 overexpression.
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Octreotide Infusion for the Treatment of Congenital Chylothorax

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Congenital chylothorax is an uncommon cause of pleural effusion in the pediatric age group, and it should be kept in consideration when evaluating a neonate with pleural effusion, as it is the commonest cause of pleural effusion in this age group (Tutor, 2014). No commonly accepted guidelines have been published so far regarding the management of congenital chylothorax in the neonate, but trials of octreotide have appeared to be promising (Bellini et al., 2018). We present a neonate with congenital chylothorax successfully treated with octreotide infusion.
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Three-Decade Evaluation of Cerebrospinal Fluid Pressure in Open-Angle Glaucoma at a Tertiary Care Center

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Elevated intraocular pressure (IOP) is the most prevalent risk factor for primary open-angle glaucoma. However, IOP alone does not fully describe a mechanical basis for disease in patients with normal tension glaucoma or primary open-angle glaucoma. The translaminar pressure difference (TLPD) theory proposes that the pressure gradient generated by the difference of IOP and cerebrospinal fluid pressure (CSFp) acting at the level of the optic nerve can lead to cupping and glaucoma when IOP is higher than normal and/or CSFp is lower than normal. The study results to date have generally supported the TLPD theory; however, varying methods, populations, and sample sizes make it difficult to compare results. To further assess whether there is an association between low CSFp and open-angle glaucoma, 30 years of cl inical data that assess 96,543 lumbar punctures were analyzed. Patients with open-angle glaucoma showed a significantly lower CSFp than randomly selected normal control patients (9.9 ± 3 mm·Hg (n = 86) versus 12.1 ± 3.6 mm·Hg (n = 114), ) following adjustment for age and sex. This retrospective study provides strong evidence for an association between open-angle glaucoma and low CSFp.
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Erosion Infiltration in the Management of Molar-Incisor Hypomineralization (MIH) Defects

Alexandros G.Sfakianakis shared this article with you from Inoreader

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White spot lesions caused by enamel demineralization are frequently encountered in dental practice. Their management has always been an important issue in modern dentistry. However, the real dilemma was treating aesthetic demands with noninvasive or minimally invasive techniques preserving the natural tissues. The introduction of resin infiltration technique seems to provide an intermediary treatment modality between prevention and restorative therapy. This case report is aimed at reporting the management of MIH opacities in anterior teeth with resin infiltration technique.
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sEMG-Based Neural Network Prediction Model Selection of Gesture Fatigue and Dataset Optimization

Alexandros G.Sfakianakis shared this article with you from Inoreader

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The fatigue energy consumption of independent gestures can be obtained by calculating the power spectrum of surface electromyography (sEMG) signals. The existing research studies focus on the fatigue of independent gestures, while the research studies on integrated gestures are few. However, the actual gesture operation mode is usually integrated by multiple independent gestures, so the fatigue degree of integrated gestures can be predicted by training neural network of independent gestures. Three natural gestures including browsing information, playing games, and typing are divided into nine independent gestures in this paper, and the predicted model is established and trained by calculating the energy consumption of independent gestures. The artificial neural networks (ANNs) including backpropagation (BP) n eural network, recurrent neural network (RNN), and long short-term memory (LSTM) are used to predict the fatigue of gesture. The support vector machine (SVM) is used to assist verification. Mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) are utilized to evaluate the optimal prediction model. Furthermore, the different datasets of the processed sEMG signal and its decomposed wavelet coefficients are trained, respectively, and the changes of error functions of them are compared. The experimental results show that LSTM model is more suitable for gesture fatigue prediction. The processed sEMG signals are appropriate for using as the training set the fatigue degree of one-handed gesture. It is better to use wavelet decomposition coefficients as datasets to predict the high-dimensional sEMG signals of two-handed gestures. The experimental results can be applied to predict the fatigue degree of complex human-machine interactive gestures, help to avoid unreasonable gestures, and improve the user's interactive experience.
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Establishment and Validation of a Prognostic Risk Model for Autophagy-Related Genes in Clear Cell Renal Cell Carcinoma

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Background. Autophagy plays an essential role in tumorigenesis. At present, due to the unclear role of autophagy in renal clear cell carcinoma, we studied the potential value of autophagy-related genes (ARGs) in renal clear cell carcinoma (ccRCC). Methods. We obtained all ccRCC data from The Cancer Genome Atlas (TCGA). We extracted the expression data of ARGs for difference analysis and carried out biological function analysis on the different results. The autophagy risk model was constructed. The 5-year survival rate was assessed using the model, and the predictive power of the model was evaluated from multiple perspectives. Cox regression analysis was use to assess whether the model could be an independent prognostic factor. Finally, the correlation between the model and clinical indicators is analyzed. Result s. The patients were divided into the high-risk group and low-risk group according to the median of autophagy risk score, and the results showed that the prognosis of the low-risk group was better than that of a high-risk group. The validation results of external data sets show that our model has good predictive value for ccRCC patients. The model can be an independent prognostic factor. Finally, the results show that our model has a stable predictive ability. Conclusion. The autophagy gene model we constructed can be used as an excellent prognostic indicator for ccRCC. Our study provides the possibility of individualized and precise treatment for ccRCC patients.
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The Composition of Gut Microbiota in Patients Bearing Hashimoto’s Thyroiditis with Euthyroidism and Hypothyroidism

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Aims. Hashimoto's thyroiditis (HT), a type of autoimmune disease, occurs due to genetic predisposition and environmental factors. It is well known that thyroid function may affect the gut microbiota. However, the composition of gut microbiota in HT patients with different thyroid function status has been less highlighted. Therefore, we focused on the alterations in the composition of gut microbiota in HT patients with euthyroidism and hypothyroidism. Methods. We performed a cross-sectional study, including 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls. Fecal samples were collected, and microbiota was examined by using 16S RNA ribosomal RNA gene sequencing. Then, we analyzed the possible pathways in relation to the enriched bacteria by linear discriminant analy sis (LDA) effect size (LEfSe). Results. Compared with the controls, bacterial richness and diversity were significantly lower in patients with HT, especially in hypothyroidism. Moreover, Lachnospiraceae_incertae_sedis, Lactonifactor, Alistipes, and Subdoligranulum were more enriched in HT patients with euthyroidism, while Phascolarctobacterium was more abundant in those with hypothyroidism. Further analysis suggested that Phascolarctobacterium was negatively related to several pathways, including environmental information processing and metabolism. Conclusion. In summary, our study demonstrated the altered composition of gut microbiota in HT patients with different thyroid function status. Moreover, Phascolarctobacterium may be involved in the development of HT.
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