The Impact of Nanomedicine on Soft Tissue Sarcoma Treated by Radiotherapy and/or Hyperthermia: A Review.

This article presents a comprehensive review of nanoparticle-assisted treatment approaches for soft tissue sarcoma (STS). STS, a heterogeneous group of mesenchymal-origin tumors with aggressive behavior and low overall survival rates, necessitates the exploration of innovative therapeutic interventions. In contrast to conventional treatments like surgery, radiotherapy (RT), hyperthermia (HT), and chemotherapy, nanomedicine offers promising advancements in STS management. This review focuses on recent research in nanoparticle applications, including their role in enhancing RT and HT efficacy through improved drug delivery systems, novel radiosensitizers, and imaging agents. Reviewing the current state of nanoparticle-assisted therapies, this paper sheds light on their potential to revolutionize soft tissue sarcoma treatment and improve patient therapy outcomes.

Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Extended Analysis of Raman Spectra Using Artificial Intelligence Techniques for Colorectal Abnormality Classification.

Raman spectroscopy (RS) techniques are attracting attention in the medical field as a promising tool for real-time biochemical analyses. The integration of artificial intelligence (AI) algorithms with RS has greatly enhanced its ability to accurately classify spectral data in vivo. This combination has opened up new possibilities for precise and efficient analysis in medical applications. In this study, healthy and cancerous specimens from 22 patients who underwent open colorectal surgery were collected. By using these spectral data, we investigate an optimal preprocessing pipeline for statistical analysis using AI techniques. This exploration entails proposing preprocessing methods and algorithms to enhance classification outcomes. The research encompasses a thorough ablation study comparing machine learning and deep learning algorithms toward the advancement of the clinical applicability of RS. The results indicate substantial accuracy improvements using techniques like baseline correction, L2 normalization, filtering, and PCA, yielding an overall accuracy enhancement of 15.8%. In comparing various algorithms, machine learning models, such as XGBoost and Random Forest, demonstrate effectiveness in classifying both normal and abnormal tissues. Similarly, deep learning models, such as 1D-Resnet and particularly the 1D-CNN model, exhibit superior performance in classifying abnormal cases. This research contributes valuable insights into the integration of AI in medical diagnostics and expands the potential of RS methods for achieving accurate malignancy classification.

Patient Dose Estimation in Computed Tomography-Guided Biopsy Procedures.

This study establishes typical Diagnostic Reference Levels (DRL) values and assesses patient doses in computed tomography (CT)-guided biopsy procedures. The Effective Dose (ED), Entrance Skin Dose (ESD), and Size-Specific Dose Estimate (SSDE) were calculated using the relevant literature-derived conversion factors. A retrospective analysis of 226 CT-guided biopsies across five categories (Iliac bone, liver, lung, mediastinum, and para-aortic lymph nodes) was conducted. Typical DRL values were computed as median distributions, following guidelines from the International Commission on Radiological Protection (ICRP) Publication 135. DRLs for helical mode CT acquisitions were set at 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass, and 9 mGy for para-aortic lymph nodes biopsies. In contrast, DRLs for biopsy acquisitions were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy, and 7.4 mGy, respectively. Median SSDE values varied from 7.6 mGy to 10 mGy for biopsy acquisitions and from 11.3 mGy to 12.6 mGy for helical scans. Median ED values ranged from 1.6 mSv to 5.7 mSv for biopsy scans and from 3.9 mSv to 9.3 mSv for helical scans. The study highlights the significance of using DRLs for optimizing CT-guided biopsy procedures, revealing notable variations in radiation exposure between helical scans covering entire anatomical regions and localized biopsy acquisitions.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Isodose surface differences: A novel tool for the comparison of dose distributions.

BACKGROUND: Comparing dose distributions is a routine task in radiotherapy, mainly in patient-specific quality assurance (PSQA). Currently, the evaluation of the dose distributions is being performed mainly with statistical methods, which could underestimate the clinical importance of the spotted differences, as per the literature. PURPOSE: This paper aims to provide proof-of-concept for a novel dose distribution comparison method based on the difference of the isodose surfaces. The new method connects acceptance tolerance to QA limitations (equipment capabilities) and integrates a clinical approach into the analysis procedure. METHODS: The distance of dose points from the isocenter can be used as a function to define the shape of an isodose surface expressed as a histogram. Isodose surface differences (ISD) are defined as the normalized differences of reference and evaluated surface histograms plotted against their corresponding isodose. Acceptance tolerances originate from actual QA tolerances and are presented clinically intuitively. The ISD method was compared to the gamma index using intentionally erroneous VMAT and IMRT plans. RESULTS: Results revealed that the ISD method is sensitive to all errors induced in the plans. Discrepancies are presented per isodose, enabling the evaluation of the plan in two regions representing PTV and Normal Tissue. ISD manages to flag errors that would remain undetected under the gamma analysis. CONCLUSION: The ISD method is a meaningful, QA-related, registration-free, and clinically oriented technique of dose distribution evaluation. This method can be used either as a standalone or an auxiliary tool to the well-established evaluation procedures, overcoming significant limitations reported in the literature.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

BACKGROUND: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). METHODS: One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. RESULTS: LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. CONCLUSION: In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

A step closer to automation: kilovoltage and Megavoltage Planar Imaging Quality Assurance, baseline, tolerance and action levels definition and exploration.

PURPOSE: To establish automated quality assurance (QA) procedures for the kilovoltage (kV) and the Megavoltage (MV) imagers of two linear accelerators (LINACS) using a commercial software. METHODS: SNC Machine™ phantoms and software were used and the baseline values, tolerance and action levels for various image quality parameters were defined. Scaling, spatial resolution, contrast, uniformity and noise were considered, explored and evaluated utilizing the appropriate phantoms and the accompanying software. kV and MV planar radiographic images, for 6MV and 10MV beams were obtained for each LINAC. For both kV and MV QA tasks, the baseline values for spatial resolution, contrast, uniformity and noise were defined. RESULTS: Subsequent measurements performed were highly reproducible and within tolerance and action levels, while noise showed variations. The calculated tolerance and action levels for noise were looser compared to the other image quality metrics. CONCLUSIONS: An automated QA workflow of the kV and MV planar radiographic mode of LINAC imagers' was established and appears to be time effective.

Predominant polarity as a neurobiological specifier in bipolar disorder: Evidence from a multimodal neuroimaging study.

BACKGROUND: While predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts. METHODS: Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons. RESULTS: Phenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an "unspecified" pattern mostly lying in-between PP-D and PP-M. CONCLUSIONS: Our multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD.

DIAGNOSTIC REFERENCE LEVELS AND COMPLEXITY INDICES IN INTERVENTIONAL RADIOLOGY.

The establishment of typical diagnostic reference levels (DRLs) values according to the complexity indices (CIs) for hepatic chemoembolisation (HC), iliac stent placement (ISP) and femoropopliteal revascularisation (FR) is reported in this study. To estimate patients' stochastic effects, effective dose was calculated through dose area product (DAP) values of this study and E/DAP conversion factors derived from the literature. Data for DAP, Reference Air Kerma (Ka,r) and fluoroscopy time (FT) were collected for 218 patients and CIs were assigned to each procedure to extract DRLs. To estimate effective dose, conversion factors and DAP values were used for seven IR procedures. DRL values for DAP were 141, 130 and 28 Gy*cm2 for HC, ISP, and FR, respectively. The corresponding DRL values for Ka,r were 634.6, 300.1 and 112.0 mGy, and for FT were 15.3, 12.4 and 17.9 min, respectively. CIs in interventional radiology are a useful tool for the optimisation of DRLs since they contribute to patient's doses.

Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA.

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137-198 MeV and Linear Energy Transfer (LET) range 1-9 keV/µm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp-1 Gy-1 for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

BACKGROUND: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. PATIENTS AND METHODS: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. RESULTS: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. CONCLUSIONS: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Nanomedicine approaches for treatment of hematologic and oncologic malignancies.

Cancer is a leading cause of death worldwide. Nowadays, the therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology and novel nanomedicine products represents an opportunity to achieve sophisticated targeting strategies and multi-functionality. Nanomedicine is increasingly used to develop new cancer diagnosis and treatment methods since this technology can modulate the biodistribution and the target site accumulation of chemotherapeutic drugs, thereby reducing their toxicity. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades while searching for a cure for cancer. Immunotherapy is revolutionizing cancer treatment, as it can achieve unprecedented responses in advanced-stage patients, including complete cures and long-term survival. A deeper understanding of the human immune system allows the establishment of combination regimens in which immunotherapy is combined with other treatment modalities (as in the case of the nanodrug Ferumoxytol). Furthermore, the combination of gene therapy approaches with nanotechnology that aims to silence or express cancer-relevant genes via one-time treatment is gradually progressing from bench to bedside. The most common example includes lipid-based nanoparticles that target VEGF-Α and KRAS pathways. This review focuses on nanoparticle-based platforms utilized in recent advances aiming to increase the efficacy of currently available cancer therapies. The insights provided and the evidence obtained in this paper indicate a bright future ahead for immuno-oncology applications of engineering nanomedicines.

Sarcopenia in patients with diabetes mellitus.

INTRODUCTION: Diseases such as diabetes mellitus may be associated with adverse changes in body composition. Sarcopenia is characterized by a progressive and generalized loss of skeletal muscle mass and functionality. AIM: To investigate the relationship between type 2 diabetes mellitus (T2DM) and sarcopenia. MATERIALS AND METHODS: In a retrospective, non-randomized study, 35 T2DM patients, aged 20-80 years, were assessed for sarcopenia prevalence compared to controls (n=16). Appendicular skeletal mass (ASM) (kg) was measured, and sarcopenia was defined as SMI <7.0 and <5.7 kg/m2, in males and females, respectively, using the European Working Group on Sarcopenia in Elderly (EWGOSP) definition. Low physical performance was defined as a walking speed of <0.8 m/s. RESULTS: Incidence of sarcopenia was significantly higher in T2DM patients vs. controls (27% vs. 20%, p=0.01) and elderly vs. young participants (40% vs. 12%, p<0.001), respectively. Walking velocity was significantly lower in T2DM patients compared to male and female controls (1.08±0.22 vs. 1.23±0.18 and 1.07±0.26 vs. 1.26±0.16, respectively, p<0.001,). CONCLUSIONS: A moderate prevalence of sarcopenia in patients with type 2 diabetes mellitus was observed, which appeared to increase significantly in older men. Finally, incidence of T2DM displayed decreased physical performance in both genders.

Implementation of TG-218 for patient-specific quality assurance tolerance and action limits determination: Gamma passing rate evaluation using 3DVH software.

PURPOSE: To determine the tolerance limit (TL) and action limit (AL) of gamma passing rates (%GP) for volumetric-modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) according to the American Association of Physicists in Medicine (AAPM) Task Group (TG)-218 recommendations, and to comparatively evaluate the clinical relevance of 2D %GP and 3D %GP. METHODS: PSQA was performed for 100 head and neck (H&N) and 73 prostate cancer VMAT treatment plans. Measurements were acquired using a cylindrical water equivalent phantom, hollow in the center, allowing measurements with homogeneous or heterogeneous inserts. The LINAC-delivered dose distributions were compared to those calculated from the treatment planning system through the gamma index. TL and AL were determined through the computation of two-dimensional (2D) %GP using the recommended acceptance criteria. Dose-volume histograms were reconstructed from the measurements using a commercially available software to detect the dosimetric errors (%DE) between the compared dose distributions. Utilizing the estimated dose on the patient anatomy, structure-specific %GP (3D %GP) were calculated. The 3D %GP were compared to the 2D %GP ones based on their correlation with the %DE. Each metric's sensitivity was determined through receiver operator characteristic analysis. RESULTS: TL and AL were in concordance with the universal ones, regarding the prostate cancer cases, but were lower for the H&N cases. Evaluation of %DE did not deem the plans unacceptable. The 2D %GP and the 3D %GP did not differ significantly regarding their correlation with %DE. For prostate plans, %GP sensitivity was higher than for H&N cases. CONCLUSIONS: Determination of institutional-specific TL and AL allows the monitoring of the PSQA procedure, yet for plans close to the limits, clinically relevant metrics should be used before they are deemed unacceptable for the process to be of higher sensitivity and efficiency.

Quantification of Nanoscale Dose Enhancement in Gold Nanoparticle-Aided External Photon Beam Radiotherapy.

The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = DoseAu/DoseWater) calculated in this study is 0.99 ± 0.01-1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.

Raman Spectroscopy: A Personalized Decision-Making Tool on Clinicians' Hands for In Situ Cancer Diagnosis and Surgery Guidance.

Accurate in situ diagnosis and optimal surgical removal of a malignancy constitute key elements in reducing cancer-related morbidity and mortality. In surgical oncology, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. Conventional imaging techniques have attempted to serve as adjuvant tools for in situ biopsy and surgery guidance. However, no single imaging modality has been proven sufficient in terms of specificity, sensitivity, multiplexing capacity, spatial and temporal resolution. Moreover, most techniques are unable to provide information regarding the molecular tissue composition. In this review, we highlight the potential of Raman spectroscopy as a spectroscopic technique with high detection sensitivity and spatial resolution for distinguishing healthy from malignant margins in microscopic scale and in real time. A Raman spectrum constitutes an intrinsic "molecular finger-print" of the tissue and any biochemical alteration related to inflammatory or cancerous tissue state is reflected on its Raman spectral fingerprint. Nowadays, advanced Raman systems coupled with modern instrumentation devices and machine learning methods are entering the clinical arena as adjunct tools towards personalized and optimized efficacy in surgical oncology.

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines.

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 µg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1ß and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1ß were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1ß release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells.

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection.

Non-alcoholic fatty liver disease (NAFLD) is an 'umbrella' term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.

Notifications and alerts in patient dose values for computed tomography and fluoroscopy-guided interventional procedures.

The terms "notifications" and "alerts" for medical exposures are used by several national and international organisations. Recommendations for CT scanners have been published by the American Association of Physicists in Medicine. Some interventional radiology societies as well as national authorities have also published dose notifications for fluoroscopy-guided interventional procedures. Notifications and alerts may also be useful for optimisation and to avoid unintended and accidental exposures. The main interest in using these values for high-dose procedures (CT and interventional) is to optimise imaging procedures, reducing the probability of stochastic effects and avoiding tissue reactions. Alerts in X-ray systems may be considered before procedures (as in CT), during procedures (in some interventional radiology systems), and after procedures, when the patient radiation dose results are known and processed. This review summarises the different uses of notifications and alerts to help in optimisation for CT and for fluoroscopy-guided interventional procedures as well as in the analysis of unintended and accidental medical exposures. The paper also includes cautions in setting the alert values and discusses the benefits of using patient dose management systems for the alerts, their registry and follow-up, and the differences between notifications, alerts, and trigger levels for individual procedures and the terms used for the collective approach, such as diagnostic reference levels. KEY POINTS: • Notifications and alerts on patient dose values for computed tomography (CT) and fluoroscopy-guided interventional procedures (FGIP) allow to improve radiation safety and contribute to the avoidance of radiation injuries and unintended and accidental exposures. • Alerts may be established before the imaging procedures (as in CT) or during and after the procedures as for FGIP. • Dose management systems should include notifications and alerts and their registry for the hospital quality programmes.