The Effects of Metformin on Obesity-Induced Diabetic Retinas

Diabetic retinopathy is a major secondary complication of type 2 diabetes. To regulate blood glucose levels in type 2 diabetic patients, metformin is popularly prescribed as an oral drug in mono- and combination therapies. Metformin was used as a responsive and preventative drug on high-fat diet (HFD) induced obese mice that emulate type 2 diabetes. Body weight was monitored weekly and systemic glucose levels including resting blood glucose levels, the glucose tolerance test, and the insulin resistance test were measured monthly. The electroretinogram (ERG) was used to measure the retinal light responses, immunohistochemistry to quantify changes in retinal protein expression, western blot to assess inflammatory markers, and fluorescein angiography to measure neovascularization. HFD-fed mice became hyperglycemic after 2 months of feeding regimen. Metformin treatment following hyperglycemia slowed body weight gain and restored systemic glucose levels to control levels. Retinal function measured by ERG showed decreased amplitudes and delayed implicit times in oscillatory potentials after 1 month of HFD and decreased amplitudes and delayed implicit times in a-wave, b-wave, and oscillatory potentials starting 2 months of HFD. Metformin treatment after 2 months of HFD was not able to restore ERG responses in HFD-fed mice. Furthermore, metformin treatment was not able to recover HFD-induced neovascularization. However, metformin treatment for the last 4 months in mice fed a HFD for 6 months was able to reduce inflammatory marker expression and the immunofluorescent proteins affected by HFD-feeding. HFD-fed mice treated with metformin from the beginning of feeding regimen as a preventative strategy not only showed slower weight gain but also do not become hyperglycemic. However, this preventative strategy did not prevent the HFD-induced retinal dysfunction measured by ERG even after 3 months of treatment. Furthermore, some HFD-induced changes in retinal protein expression began after 1 month of HFD-treatment, but metformin treatment concurrent with HFD was not able to prevent HFD-induced changes

Identifying neural mechanisms and behavioral effects of anxiety on attentional capture

Attention research has long investigated the mechanisms by which sensory information is selectively filtered for neural representation. Models for visual selective attention initially formed a theoretical dichotomy in which goal-oriented or salience-driven mechanisms were argued as the predominant modes for attentional selection. However, this theoretical dichotomy was challenged when new experimental findings could not be reduced to goal-oriented or salience-driven mechanisms. These results were grouped into a new component of attentional control by an experience-driven mechanism and expanded models of selective attention into a theoretical trichotomy under the third label selection history. In the context of attention research, threat has been investigated primarily by measuring rapid orienting towards threatening stimuli. Individuals with elevated state anxiety measured via self-report demonstrate increased attentional orienting towards threatening stimuli and enhanced attentional capture by physically salient stimuli. However, such findings are limited to attentional mechanisms toward the threatening nature of a stimulus and do not extend to more systemic changes in attentional control when the observer is in a threatened state. It is yet unknown whether elevated state anxiety globally modulates attentional capture through a core mechanism or whether such changes in observer state uniquely modulate different modes of attentional control. Furthermore, the mechanism by which threatening stimuli are afforded greater attentional priority in individuals with elevated state anxiety is still unclear. In this dissertation, I investigate how attentional priority can be modulated by changing the state of an individual by experimentally inducing anxiety through the Threat of Shock (ToS) paradigm. I first present a series of behavior experiments that investigate how unpredictable threat modulates the three predominant mechanisms of attentional selection: attentional capture by reward history (selection history), color (salience-driven), and strategic goals. Then, I present a neuroimaging experiment that investigates how the neural mechanisms of processing threat interacts with mechanisms of attentional selection by previously-reward associated stimuli. I conclude by expanding on the core findings of this dissertation and its implications concerning how changes in observer state modulates attentional control and how the identified mechanisms can be expanded to inform our understanding of attentional biases toward threatening stimuli

Smart laser Sintering: Deep Learning-Powered powder bed fusion 3D printing in precision medicine

© 2024 The Author(s). Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Medicines remain ineffective for over 50% of patients due to conventional mass production methods with fixed drug dosages. Three-dimensional (3D) printing, specifically selective laser sintering (SLS), offers a potential solution to this challenge, allowing the manufacturing of small, personalized batches of medication. Despite its simplicity and suitability for upscaling to large-scale production, SLS was not designed for pharmaceutical manufacturing and necessitates a time-consuming, trial-and-error adaptation process. In response, this study introduces a deep learning model trained on a variety of features to identify the best feature set to represent drugs and polymeric materials for the prediction of the printability of drug-loaded formulations using SLS. The proposed model demonstrates success by achieving 90% accuracy in predicting printability. Furthermore, explainability analysis unveils materials that facilitate SLS printability, offering invaluable insights for scientists to optimize SLS formulations, which can be expanded to other disciplines. This represents the first study in the field to develop an interpretable, uncertainty-optimized deep learning model for predicting the printability of drug-loaded formulations. This paves the way for accelerating formulation development, propelling us into a future of personalized medicine with unprecedented manufacturing precision.Peer reviewe

Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging

Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG) ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.11248Ysciescopu

Acute Respiratory Distress Syndrome after Rotavirus Infection in a C1q Nephropathy Patient: A Case Report

C1q nephropathy is a rare glomerulopathy that typically presents with nephrotic syndrome in children. Treatment with immunosuppressive agents renders patients vulnerable to infection and its complications. Gastroenteritis is common in children, and rotavirus is a leading cause. Extraintestinal manifestations of rotavirus have recently been reported; however, there is a paucity of cases exploring the involvement of a rotavirus on the respiratory system. Acute respiratory distress syndrome (ARDS) is a rapid onset respiratory failure characterized by noncardiogenic pulmonary edema and hypoxemia. Causes of ARDS include sepsis, pneumonia, pancreatitis, aspiration, and trauma. In this paper, we report a case of ARDS after rotavirus infection in a child with C1q nephropathy who had been treated with immunosuppressive agents

Extraskeletal Calcifications in Children with Maintenance Peritoneal Dialysis

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, often accompanied by extra-skeletal calcification in adult patients. As increased vascular calcification is predicted to increase cardiovascular mortality and morbidity, the revised Kidney Disease: Improving Global Outcomes guidelines recommend avoiding calcium-containing phosphate chelators. However, extra-skeletal calcification is less commonly noticed in pediatric patients. Here, we report our experience of such a complication in pediatric patients receiving maintenance peritoneal dialysis. Extra-skeletal calcification was noticed at the corneas, pelvic cavity, and soft tissues of the lower leg in 4 out of 32 patients on maintenance peritoneal dialysis. These patients experienced the aggravation of extra-skeletal calcifications during peritoneal dialysis, and 2 of them underwent excisional operations. It is required to monitor extra-skeletal calcifications in children on kidney replacement therapy

Deletion of miR-150 Exacerbates Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic Mice

Diabetic retinopathy (DR) is the leading cause of blindness among American adults above 40 years old. The vascular complication in DR is a major cause of visual impairment, making finding therapeutic targets to block pathological angiogenesis a primary goal for developing DR treatments. MicroRNAs (miRs) have been proposed as diagnostic biomarkers and potential therapeutic targets for various ocular diseases including DR. In diabetic animals, the expression levels of several miRs, including miR-150, are altered. The expression of miR-150 is significantly suppressed in pathological neovascularization in mice with hyperoxia-induced retinopathy. The purpose of this study was to investigate the functional role of miR-150 in the development of retinal microvasculature complications in high-fat-diet (HFD) induced type 2 diabetic mice. Wild type (WT) and miR-150 null mutant (miR-150-/-) male mice were given a HFD (59% fat calories) or normal chow diet. Chronic HFD caused a decrease of serum miR-150 in WT mice. Mice on HFD for 7 months (both WT and miR-150-/-) had significant decreases in retinal light responses measured by electroretinograms (ERGs). The retinal neovascularization in miR-150-/--HFD mice was significantly higher compared to their age matched WT-HFD mice, which indicates that miR-150 null mutation exacerbates chronic HFD-induced neovascularization in the retina. Overexpression of miR-150 in cultured endothelial cells caused a significant reduction of vascular endothelial growth factor receptor 2 (VEGFR2) protein levels. Hence, deletion of miR-150 significantly increased the retinal pathological angiogenesis in HFD induced type 2 diabetic mice, which was in part through VEGFR2

Recent Advances in Ultrasound and Photoacoustic Analysis for Thyroid Cancer Diagnosis

Abstract Thyroid cancer is one of the most commonly diagnosed cancers worldwide, with a continuously increasing incidence rate in recent decades. Although ultrasonography, which is the current screening method in clinical workflows, has successfully triaged cancerous nodules for biopsy, overdiagnosis has also grown due to the relatively low specificity of the method. Studies are conducted to overcome this overdiagnosis issue by complementing ultrasonography with additional image‐based analysis techniques. This review presents an overview of the current advances in clinical trials using advanced ultrasound (US) and photoacoustic (PA) imaging techniques for thyroid nodules in humans. A summary of initial trials by Doppler US and US elastography to improve the classification accuracy of thyroid nodules is presented. Furthermore, recent PA techniques with multispectral analyses utilizing clinically available machines are explored. By amending the existing ultrasonography, the advanced US and PA techniques can enhance the triaging accuracy by analyzing both structural and functional information of thyroid nodules in vivo