A Multi-Stage Approach for Cardiovascular Risk Assessment from Retinal Images Using an Amalgamation of Deep Learning and Computer Vision Techniques.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Early detection and effective risk assessment are crucial for implementing preventive measures and improving patient outcomes for CVDs. This work presents a novel approach to CVD risk assessment using fundus images, leveraging the inherent connection between retinal microvascular changes and systemic vascular health. This study aims to develop a predictive model for the early detection of CVDs by evaluating retinal vascular parameters. This methodology integrates both handcrafted features derived through mathematical computation and retinal vascular patterns extracted by artificial intelligence (AI) models. By combining these approaches, we seek to enhance the accuracy and reliability of CVD risk prediction in individuals. The methodology integrates state-of-the-art computer vision algorithms and AI techniques in a multi-stage architecture to extract relevant features from retinal fundus images. These features encompass a range of vascular parameters, including vessel caliber, tortuosity, and branching patterns. Additionally, a deep learning (DL)-based binary classification model is incorporated to enhance predictive accuracy. A dataset comprising fundus images and comprehensive metadata from the clinical trials conducted is utilized for training and validation. The proposed approach demonstrates promising results in the early prediction of CVD risk factors. The interpretability of the approach is enhanced through visualization techniques that highlight the regions of interest within the fundus images that are contributing to the risk predictions. Furthermore, the validation conducted in the clinical trials and the performance analysis of the proposed approach shows the potential to provide early and accurate predictions. The proposed system not only aids in risk stratification but also serves as a valuable tool for identifying vascular abnormalities that may precede overt cardiovascular events. The approach has achieved an accuracy of 85% and the findings of this study underscore the feasibility and efficacy of leveraging fundus images for cardiovascular risk assessment. As a non-invasive and cost-effective modality, fundus image analysis presents a scalable solution for population-wide screening programs. This research contributes to the evolving landscape of precision medicine by providing an innovative tool for proactive cardiovascular health management. Future work will focus on refining the solution's robustness, exploring additional risk factors, and validating its performance in additional and diverse clinical settings.

Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization.

Nicotinamide N-methyltransferase (Nnmt) methylates nicotinamide, a form of vitamin B3, to produce N(1)-methylnicotinamide (MNAM). Nnmt has emerged as a metabolic regulator in adipocytes, but its role in the liver, the tissue with the strongest Nnmt expression, is not known. In spite of its overall high expression, here we find that hepatic expression of Nnmt is highly variable and correlates with multiple metabolic parameters in mice and humans. Further, we find that suppression of hepatic Nnmt expression in vivo alters glucose and cholesterol metabolism and that the metabolic effects of Nnmt in the liver are mediated by its product MNAM. Supplementation of high-fat diet with MNAM decreases serum and liver cholesterol and liver triglycerides levels in mice. Mechanistically, increasing Nnmt expression or MNAM levels stabilizes sirtuin 1 protein, an effect that is required for their metabolic benefits. In summary, we describe here a novel regulatory pathway for vitamin B3 that could provide a new opportunity for metabolic disease therapy.

Expression of melanin-concentrating hormone receptor 2 protects against diet-induced obesity in male mice.

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide that is a ligand for two subtypes of MCH receptors, MCHR1 and MCHR2. MCHR1 is universally expressed in mammals ranging from rodents to humans, but the expression of MCHR2 is substantially restricted. In mammals, MCHR2 has been defined in primates as well as other species such as cats and dogs but is not seen in rodents. Although the role of MCHR1 in mediating the actions of MCH on energy balance is clearly defined using mouse models, the role of MCHR2 is harder to characterize because of its limited expression. To determine any potential role of MCHR2 in energy balance, we generated a transgenic MCHR1R2 mouse model, where human MCHR2 is coexpressed in MCHR1-expressing neurons. As shown previously, control wild-type mice expressing only native MCHR1 developed diet-induced obesity when fed a high-fat diet. In contrast, MCHR1R2 mice had lower food intake, leading to their resistance to diet-induced obesity. Furthermore, we showed that MCH action is altered in MCHR1R2 mice. MCH treatment in wild-type mice inhibited the activation of the immediate-early gene c-fos, and coexpression of MCHR2 reduced the inhibitory actions of MCHR1 on this pathway. In conclusion, we developed an experimental animal model that can provide insight into the action of MCHR2 in the central nervous system and suggest that some actions of MCHR2 oppose the endogenous actions of MCHR1.

Methionine and choline regulate the metabolic phenotype of a ketogenic diet.

Low-carbohydrate ketogenic diets are commonly used as weight loss alternatives to low-fat diets, however the physiological and molecular adaptations to these diets are not completely understood. It is assumed that the metabolic phenotype of the ketogenic diet (KD) is caused by the absence of carbohydrate and high fat content, however in rodents the protein content of KD affects weight gain and ketosis. In this study we examined the role of methionine and choline in mediating the metabolic effects of KD. We have found that choline was more effective than methionine in decreasing the liver steatosis of KD-fed mice. On the other hand, methionine supplementation was more effective than choline in restoring weight gain and normalizing the expression of several fatty acid and inflammatory genes in the liver of KD-fed mice. Our results indicate that choline and methionine restriction rather than carbohydrate restriction underlies many of the metabolic effects of KD.

Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis.

OBJECTIVES: We sought to develop a novel model of central venous catheter (CVC)-associated candidiasis in mice and to use this model to examine the efficacy of caspofungin to treat and prevent Candida albicans biofilms in vivo. METHODS: We used catheterized mice, commercially available from the National Cancer Institute, to form C. albicans biofilms inside CVCs. Once the model was developed, we examined the efficacy of caspofungin for the treatment of preformed biofilms and for the prevention of C. albicans biofilm formation. RESULTS: We developed a relatively simple murine model of CVC-associated candidiasis that minimized the number of manipulations necessary for in vivo biofilm formation. C. albicans biofilms formed in vivo display structural features similar to those observed for models of in vitro- and other in vivo-formed biofilms. Following model development, 0.25 microg/mL of caspofungin was instilled in the catheter to treat preformed biofilms. The results indicated that caspofungin treatment significantly reduced biofilm fungal load in the catheters and dissemination to kidneys compared with untreated controls. In a second set of experiments catheters were pre-treated by filling with 60 microg/mL of caspofungin before challenge with C. albicans via the CVC. Again, the results indicated a significant reduction in biofilm fungal load and dissemination to kidneys compared with untreated controls. CONCLUSIONS: We have developed a novel model of CVC-associated candidiasis in mice. Using this model we demonstrate the efficacy of caspofungin for the treatment and prevention of C. albicans biofilms in vivo.