Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion.

PURPOSE: To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser-induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. METHODS: A reliable and reproducible model of laser-induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX-4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age-matched control retinas were analyzed using qRT-PCR. RESULTS: Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL-positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT-PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia. CONCLUSIONS: This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia-related neuronal cell damage. PERSPECTIVES: Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO.

Classification of clinically actionable genetic mutations in cancer patients.

Personalized medicine in cancer treatment aims to treat each individual's cancer tumor uniquely based on the genetic sequence of the cancer patient and is a much more effective approach compared to traditional methods which involve treating each type of cancer in the same, generic manner. However, personalized treatment requires the classification of cancer-related genes once profiled, which is a highly labor-intensive and time-consuming task for pathologists making the adoption of personalized medicine a slow progress worldwide. In this paper, we propose an intelligent multi-class classifier system that uses a combination of Natural Language Processing (NLP) techniques and Machine Learning algorithms to automatically classify clinically actionable genetic mutations using evidence from text-based medical literature. The training data set for the classifier was obtained from the Memorial Sloan Kettering Cancer Center and the Random Forest algorithm was applied with TF-IDF for feature extraction and truncated SVD for dimensionality reduction. The results show that the proposed model outperforms the previous research in terms of accuracy and precision scores, giving an accuracy score of approximately 82%. The system has the potential to revolutionize cancer treatment and lead to significant improvements in cancer therapy.

Neuro-dermatological association between psoriasis and depression: an immune-mediated inflammatory process validating skin-brain axis theory.

OBJECTIVE: Our study's motive was to recognize various immune-mediated inflammatory processes involved in the pathogenesis of depression and psoriasis and interlink between them based on inflammatory mediators. METHODS: A careful and comprehensive literature search was done through various databases like PubMed, Google Scholar, and EBSCO. A total of 56 studies were included in our study after careful screening. RESULTS: The immune-mediated inflammatory process was significantly associated with the pathogenesis of both depression and psoriasis. Most of the inflammatory markers involved in Psoriasis (TNF-α, IL-2, IL-6, IL-23, IL-1ß, IL-10), and increased serotonin transporters (5-HTT) were also found in the pathogenesis of depression, showing the immune-inflammatory linkage between psoriasis and major depression. Based on immune chemistry, the levels of CD2+, CD4+, CD8+ T-lymphocytes were also found to be raised in both depression and psoriasis, validating their relationship. Hyperactivity of HPA-axis was also found another interlink between them along with reduced melatonin amount. CONCLUSIONS: According to various studies, the neuro-dermatological association between psoriasis and depression is significant. Different immune markers involved in the pathogenesis of depression and psoriasis also show the bidirectional association between them. However, this association between psoriasis and depression is positively correlated, but more work is required to answer why all depressed patients fail to develop psoriasis and why all psoriatic patients fail to develop depression.

Evaluation of triclosan exposures on secretion of pro-inflammatory cytokines from human immune cells.

Triclosan (TCS) is widely used in personal hygiene products, such as mouthwash and toothpaste, and is found in human tissues. Interleukin (IL)-1 beta (IL-1ß), IL-6, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) are pro-inflammatory cytokines and inappropriately elevated levels of each have been associated with pathologies including rheumatoid arthritis and certain cancers. Here we examine effects of TCS on the secretion of the pro-inflammatory cytokines from human immune cell preparations. TCS at concentrations between 0.05-5 µM consistently increased the secretion of IL-1ß, IL-6, and TNFα within 24 h of exposure and the increases often maintained out to 6 days of exposure. TCS also induced increases in IFNγ secretion, however the increases were most consistent after 48 h of exposure rather than within 24 h. Additionally, a role for both p44/42 and p38 MAPK in TCS-stimulated increases in IL-1ß was seen in cells from some donors.

A novel method for visualizing and tracking endogenous mRNA in a specific cell population in pathological neovascularization.

Diabetic retinopathy, retinopathy of prematurity and retinal vein occlusion are potentially blinding conditions largely due to their respective neovascular components. The development of real-time in vivo molecular imaging methods, to assess levels of retinal neovascularization (NV), would greatly benefit patients afflicted with these conditions. mRNA hybridization techniques offer a potential method to image retinal NV. The success of these techniques hinges on the selection of a target mRNA whose tissue levels and spatial expression patterns correlate closely with disease burden. Using a model of oxygen-induced retinopathy (OIR), we previously observed dramatic increases in retinal endoglin that localized to neovascular structures (NV), directly correlating with levels of neovascular pathology. Based on these findings, we have investigated Endoglin mRNA as a potential marker for imaging retinal NV in OIR mice. Also of critical importance, is the application of innovative technologies capable of detecting mRNAs in living systems with high sensitivity and specificity. To detect and visualize endoglin mRNA in OIR mice, we have designed and synthesized a novel imaging probe composed of short-hairpin anti-sense (AS) endoglin RNA coupled to a fluorophore and black hole quencher (AS-Eng shRNA). This assembly allows highly sensitive fluorescence emission upon hybridization of the AS-Eng shRNA to cellular endoglin mRNA. The AS-Eng shRNA is further conjugated to a diacyl-lipid (AS-Eng shRNA-lipid referred to as probe). The lipid moiety binds to serum albumin facilitating enhanced systemic circulation of the probe. OIR mice received intraperitoneal injections of AS-Eng shRNA-lipid. Ex vivo imaging of their retinas revealed specific endoglin mRNA dependent fluorescence superimposed on neovascular structures. Room air mice receiving AS-Eng shRNA-lipid and OIR mice receiving a non-sense control probe showed little fluorescence activity. In addition, we found that cells in neovascular lesions labelled with endoglin mRNA dependent fluorescence, co-labelled with the macrophage/microglia-associated marker IBA1. Others have shown that cells expressing macrophage/microglia markers associate with retinal neovascular structures in proportion to disease burden. Hence we propose that our probe may be used to image and to estimate the levels of retinal neovascular disease in real-time in living systems.

A systematic review of non-trunk basilar perforator aneurysms: is it worth chasing the small fish?

BACKGROUND AND PURPOSE: Non-trunk basilar artery perforator aneurysms (BAPAs) are rare intracranial vascular pathologies that have long been underdiagnosed, under-reported, and under-analyzed. We performed a systematic review of the efficacy and safety endpoints between conservative and active treatment approaches for non-trunk BAPAs. METHODS: Major databases were analyzed for relevant publications between 1995 and 2019. Studies comparing the outcomes between conservative and active treatment approaches such as coiling, stenting, clipping, liquid embolization, and flow diversion were included. Mortality rate, rate of permanent neurological deficit as determined by the modified Rankin Score (mRS), rate of second treatment occurrence, and perioperative complication rate were also assessed. RESULTS: A total of 24 studies, including 54 patients with 56 non-trunk BAPAs, were included. The mean maximum aneurysm diameter was 2.70 mm (range 1-10). A diagnosis was achieved with the initial DSA in 50.0% (27/54) of the patients. A conservative approach was used in 16 patients while active treatment was used in the other 38. Thirteen of 15 (86.7%) patients in the conservative group and 27/34 (79.4%) in the active treatment group had an mRS score 0-2. A non-significant higher odds of a positive outcome was observed in the conservative group (OR 1.51, 95% CI 0.50 to 4.54). The event-related mortality rate was 3.55% (3/54) with one procedure-related death in the active treatment group. CONCLUSIONS: In patients with non-trunk BAPAs unamenable to active treatment, conservative approaches may result in acceptable functional outcomes and low morbidity. Small sample sizes and under-reporting of outcomes warrant further study.