Oncotic (Myxomatous) Aneurysms: A Review of Management

Atrial myxomas are the most common primary cardiac tumors and may manifest with neurological symptoms in ∼ 30% of cases. Cerebral ischemia, aneurysmal formation, and extravascular metastases are mechanisms that lead to these neurological manifestations. Perilesional changes on computed tomography (CT) and magnetic resonance imaging (MRI) may help in the diagnosis of myxomatous aneurysms, which are usually located in the distal middle cerebral artery (MCA) and in the posterior cerebral artery (PCA) circulation territories. Careful resection of the cardiac lesion is essential for preventing embolism. However, treatment of myxomatous aneurysms is controversial due to the limited understanding of the natural history of this condition. Treatment may include clinical observation in asymptomatic patients, surgical resection, endovascular approaches, adjuvant chemotherapy, and low-dose radiation therapy. We present one case of a female patient with myxomatous aneurysm secondary to an atrial myxoma who presented with neurological symptoms and another case of a female patient who developed neurological symptoms after initial surgical treatment of the primary lesion. Lesion growth rate, topography, morphology, and the patient's clinical condition must be considered when choosing a therapeutical method. Further clinical studies are needed to achieve a better understanding and treatment of this disease.

High Plus Low Dose Radiation Strategy in Combination with TIGIT and PD1 Blockade to Promote Systemic Antitumor Responses

Tumors deploy various immune-evasion mechanisms that create a suppressive environment and render effector T-cells exhausted and inactive. Therefore, a rational utilization of checkpoint inhibitors may alleviate exhaustion and may partially restore antitumor functions. However, in high-tumor-burden models, the checkpoint blockade fails to maintain optimal efficacy, and other interventions are necessary to overcome the inhibitory tumor stroma. One such strategy is the use of radiotherapy to reset the tumor microenvironment and maximize systemic antitumor outcomes. In this study, we propose the use of anti-PD1 and anti-TIGIT checkpoint inhibitors in conjunction with our novel RadScopal technique to battle highly metastatic lung adenocarcinoma tumors, bilaterally established in 129Sv/Ev mice, to mimic high-tumor-burden settings. The RadScopal approach is comprised of high-dose radiation directed at primary tumors with low-dose radiation delivered to secondary tumors to improve the outcomes of systemic immunotherapy. Indeed, the triple therapy with RadScopal + anti-TIGIT + anti-PD1 was able to prolong the survival of treated mice and halted the growth of both primary and secondary tumors. Lung metastasis counts were also significantly reduced. In addition, the low-dose radiation component reduced TIGIT receptor (PVR) expression by tumor-associated macrophages and dendritic cells in secondary tumors. Finally, low-dose radiation within triple therapy decreased the percentages of TIGIT+ exhausted T-cells and TIGIT+ regulatory T-cells. Together, our translational approach provides a new treatment alternative for cases refractory to other checkpoints and may bring immunotherapy into a new realm of systemic disease control.

U(VI) Adsorption onto Low Dose Radiation Acclimated Tradescantia Fluminensis

The plants that long-term grown in radiation area could be acclimated by low dose radiation (LDR). In this paper, LDR acclimated Tradescantia fluminensis (Commelinaceae) was first collected as a biomass adsorbent towards uranium adsorption. Comparative experiments verified the potential radiation effects of LDR acclimation, moreover, qe values of the wild and LDR acclimated Tradescantia fluminensis were ~16 mg/g and 20 mg/g, respectively. U(VI) adsorption amount gradually reached equilibrium after 180 min shaking, and the adsorption process described well by the pseudo-second-order model. However, ionic strength has no obvious effect on the qe values. SEM and TG-DSC suggested good structural stability of LDR acclimated Tradescantia fluminensis during the U(VI) adsorption process. FTIR and XPS verfied the surface coordination of U(VI) via -OH and -COOH groups on LDR acclimated Tradescantia fluminensis surface, and the increasing amounts of the two groups could account for the improved U(VI) adsorption capacity compared to the wild Tradescantia fluminensis. Our present work can indicate that LDR acclimation could be a novel way to obtain biomass adsorbents for U(VI) removal from aqueous solutions.

Evaluation of Global DNA Methylation and Gene Expression of Izumo1 and Izumo1r in Gonads after High- and Low-Dose Radiation in Neonatal Mice

The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed in stages during their maturity. Furthermore, the binding of Izumo on the surface of sperm and Juno on the surface of oocytes is essential for fertilization. Thus, there is a possibility that these genes are useful indicators to evaluate fertility in mice after irradiation exposure. Therefore, in this study, we analyzed global DNA methylation patterns in the testes and gene expression of Izumo1 and Izumo1r (Juno) in the gonads of mice after neonatal acute high-dose ionizing radiation (HDR) and chronic low-dose ionizing radiation (LDR). One-week-old male and female mice were irradiated with a total dose of 4 Gy, with acute HDR at 7 days at a dose rate of 30 Gy/h and LDR continuously at a dose rate of 6 mGy/h from 7 to 35 days. Their gonads were subsequently analyzed. The results of global DNA methylation patterns in the testes showed that methylation level increased with age in the control group, the LDR group maintained its DNA methylation level, and the HDR group showed decreased DNA methylation levels with age. In the control group, the gene expression level of Izumo1 in the testis did not show age-related changes, although there was high expression at 100 days of age. However, in the LDR group, the expression level recovered after the end of irradiation, while it remained low regardless of age in the HDR group. Conversely, gene expression of Izumo1r (Izumo1 receptor) in the ovary decreased with age in the control group. Although the gene expression of Izumo1r decreased with age in the LDR group, it remained low in the HDR group. Our results indicate that LDR can induce different DNA methylation patterns, and both high- and low-dose radiation before sexual maturity might affect gametogenesis and fertility.

Comparative analysis of population mortality in the cities of Severodvinsk and Arkhangelsk

Increasing use of ionizing radiation sources in different spheres of human life dictates the need for investigating the effects of low-dose radiation on mortality and morbidity. The aim of this study was to compare mortality from the most common non-communicable diseases in the cities of Severodvinsk and Arkhangelsk. We analyzed the rates of age- and sex-specific mortality from circulatory system diseases (CSD), malignancies, digestive system disorders, respiratory system diseases, and external causes. CSD-related mortality among men and women past working age was higher in Severodvinsk than in Arkhangelsk (median (Q1; Q3): 3,349 (3,271; 3,458) vs 2,651 (2,618; 2,756), p < 0.012; 1,947 (1,890; 2,022) vs 1,753 (1,727; 1,809), p < 0.012; 292 (281; 342) vs 265 (253; 274), p < 0.025, respectively). For other causes of death, mortality rates in Severodvinsk did not exceed those in Arkhangelsk. Increased mortality from CSD in Severodvinsk cannot be linked to socioeconomic conditions or chemical air pollution because the standard of living is higher in Severodvinsk than in Arkhangelsk, whereas the level of chemical pollution is lower. At the same time, the presence of the nuclear shipyard and radioactive waste repository in Severodvinsk could cause chronic exposure to low-dose radiation. It is important to expand preventive measures aimed at early detection of vascular damage in nuclear workers and general groups of population residing in the vicinity of hazardous radiation sites.

Injectable Hydrogel for Synergetic Low Dose Radiotherapy, Chemodynamic Therapy and Photothermal Therapy

Higher doses of radiotherapy (RT) are associated with resistance induction, therefore highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation. Our FH can deliver FeGA directly to the tumor site via intratumoral injection, where it is a reservoir-based system to conserve FeGA. The photothermal properties of FeGA steadily dissolve FH under laser irradiation, and, simultaneously, FeGA reacts with a large amount of H2O2 in the cell to produce OH (Fenton reaction) which is highly toxic to mitochondria, rendering the cell inactive and reducing radiotherapy resistance. In vivo and in vitro studies suggest that combining the FH and NIR irradiation with RT (2Gy) can significantly reduce tumor proliferation without side effects such as inflammation. To conclude, this is the first study to achieve combined chemodynamic therapy (CDT) and photothermal therapy (PTT) in situ treatment, and the best therapeutic effect can be obtained with a low-dose radiation combination, thus expanding the prospects of FeGA-based tumor therapy.