Chronic inflammation in a radium dial painter cohort: elevated neutrophil to lymphocyte ratio and radiation-induced hearing loss.

The radium dial painters (RDP) are a well-described group of predominantly young women who incidentally ingested 226Ra and 228Ra as they painted luminescent watch dials in the first part of the twentieth century. In 1974 pathologist Dr. William D.

Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications.

The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications.

Reactive astrocytes generated from human iPSC are pro-inflammatory and display altered metabolism.

Astrocytes are the most abundant type of glial cell in the central nervous system and they play pivotal roles in both normal health and disease. Their dysfunction is detrimental to many brain related pathologies. Under pathological conditions, such as Alzheimer's disease, astrocytes adopt an activated reactive phenotype which can contribute to disease progression.

CD4 T cell-associated cytokines induce a chronic pro-inflammatory phenotype in induced pluripotent stem cell-derived midbrain astrocytes.

Astrocytes are mediators of homeostasis but contribute to neuroinflammation in Parkinson's disease (PD). Mounting evidence suggests involvement of peripheral immune cells in PD pathogenesis. Therefore, this study aimed to determine the potential role of peripheral immune secreted cytokines in modulating midbrain astrocyte reactivity.

Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility.

Misclassification of causes of death among a small all-autopsied group of former nuclear workers: Death certificates vs. autopsy reports.

The U.S. Transuranium and Uranium Registries performs autopsies on each of its deceased Registrants as a part of its mission to follow up occupationally-exposed individuals.

Human stem cell-derived ventral midbrain astrocytes exhibit a region-specific secretory profile.

This scientific commentary refers to 'Human stem cell-derived astrocytes exhibit region-specific heterogeneity in their secretory profiles', by Clarke (https://doi.org/10.1093/brain/awaa258) in Brain.

Human Brain-Based Models Provide a Powerful Tool for the Advancement of Parkinson's Disease Research and Therapeutic Development.

Parkinson's disease (PD) is the second most common neurodegenerative disease and affects approximately 2-3% of the population over the age of 65. PD is characterised by the loss of dopaminergic neurons from the substantia nigra, leading to debilitating motor symptoms including bradykinesia, tremor, rigidity, and postural instability. PD also results in a host of non-motor symptoms such as cognitive decline, sleep disturbances and depression.

Plutonium in Manhattan Project workers: Using autopsy data to evaluate organ content and dose estimates based on urine bioassay with implications for radiation epidemiology.

Purpose: Radiation dose estimates in epidemiology typically rely on intake predictions based on urine bioassay measurements. The purpose of this article is to compare the conventional dosimetric estimates for radiation epidemiology with the estimates based on additional post-mortem tissue radiochemical analysis results.

Methods: The comparison was performed on a unique group of 11 former Manhattan Project nuclear workers, who worked with plutonium in the 1940s, and voluntarily donated their bodies to the United States Transuranium and Uranium Registries.

Efficient and Scalable Generation of Human Ventral Midbrain Astrocytes from Human-Induced Pluripotent Stem Cells.

In Parkinson's disease, progressive dysfunction and degeneration of dopamine neurons in the ventral midbrain cause life-changing symptoms. Neuronal degeneration has diverse causes in Parkinson's, including non-cell autonomous mechanisms mediated by astrocytes. Throughout the CNS, astrocytes are essential for neuronal survival and function, as they maintain metabolic homeostasis in the neural environment.

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

Parkinson's disease (PD), the second most common neurodegenerative disease, is characterised by the motor symptoms of bradykinesia, rigidity and resting tremor and non-motor symptoms of sleep disturbances, constipation, and depression. Pathological hallmarks include neuroinflammation, degeneration of dopaminergic neurons in the substantia nigra pars compacta, and accumulation of misfolded α-synuclein proteins as intra-cytoplasmic Lewy bodies and neurites. Microglia and astrocytes are essential to maintaining homeostasis within the central nervous system (CNS), including providing protection through the process of gliosis.

Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications.

This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel.

A Monte Carlo t Test to Evaluate Mesothelioma and Radiation in the US Transuranium and Uranium Registries.

A cluster of nine mesothelioma cases was observed among 341 registrants' deaths in the US Transuranium and Uranium Registries. Descriptive analysis showed that mesothelioma cases had the highest average cumulative external radiation dose compared with lung cancer, other cancer, and noncancer deaths. Further analysis indicated that the mesothelioma cluster was very different demographically from lung cancer, other cancer, and noncancer deaths.

Validation of a system of models for plutonium decorporation therapy.

A recently proposed system of models for plutonium decorporation (SPD) was developed using data from an individual occupationally exposed to plutonium via a wound [from United States Transuranium and Uranium Registries (USTUR) Case 0212]. The present study evaluated the SPD using chelation treatment data, urine measurements, and post-mortem plutonium activities in the skeleton and liver from USTUR Case 0269. This individual was occupationally exposed to moderately soluble plutonium via inhalation and extensively treated with chelating agents.

Improved Modeling of Plutonium-DTPA Decorporation.

Individuals with significant intakes of plutonium (Pu) are typically treated with chelating agents, such as the trisodium salt form of calcium diethylenetriaminepentaacetate (CaNa-DTPA, referred to hereafter as Ca-DTPA). Currently, there is no recommended approach for simultaneously modeling plutonium biokinetics during and after chelation therapy. In this study, an improved modeling system for plutonium decorporation was developed.

Ustur Case 0846: Modeling Americium Biokinetics after Intensive Decorporation Therapy.

Decorporation therapy with salts of diethylenetriamine-pentaacetic acid binds actinides, thereby limiting uptake to organs and enhancing the rate at which actinides are excreted in urine. International Commission on Radiological Protection reference biokinetic models cannot be used to fit this enhanced exertion simultaneously with the baseline actinide excretion rate that is observed prior to the start of therapy and/or after the effects of therapy have ceased. In this study, the Coordinated Network on Radiation Dosimetry approach, which was initially developed for modeling decorporation of plutonium, was applied to model decorporation of americium using data from a former radiation worker who agreed to donate his body to the US Transuranium and Uranium Registries for research.

Generation of defined neural populations from pluripotent stem cells.

Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS).

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes.

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes.

The Pseudo-Pelger huët Cell as a Retrospective Dosimeter: Analysis of a Radium Dial Painter Cohort.

Recently, the pseudo-Pelger Huët anomaly in peripheral blood neutrophils has been described as a new radiation-induced, stable biomarker. In this study, pseudo-Pelger Huët anomaly was examined in peripheral blood slides from a cohort of 166 former radium dial painters and ancillary personnel in the radium dial industry, 35 of whom had a marrow dose of zero above background. Members of the radium dial painter cohort ingested Ra and Ra at an early age (average age 20.

US Transuranium and Uranium Registries case study on accidental exposure to uranium hexafluoride.

The United States Transuranium and Uranium Registries' (USTUR) whole-body donor (Case 1031) was exposed to an acute inhalation of uranium hexafluoride (UF6) produced from an explosion at a uranium processing plant 65 years prior to his death. The USTUR measurements of tissue samples collected at the autopsy indicated long-term retention of inhaled slightly enriched uranium material (0.85% (235)U) in the deep lungs and thoracic lymph nodes.

Carcinogenic and inflammatory effects of plutonium-nitrate retention in an exposed nuclear worker and beagle dogs.

Purpose: Plutonium-nitrate has a moderately rapid translocation rate from the lung to blood stream. Previous studies have shown an unexpected retention of soluble plutonium in the beagles and human case studied here. The inflammatory responses that may be associated with long-term exposure to ionizing radiation were characterized.

Corrupted cultures in mental health inpatient settings. Is restraint reduction the answer?

The early years of the 21st century have seen successful efforts in a number of countries to reduce the use of restraint in services for people with mental health problems. An underlying emphasis on 'cultural change' is characteristic of such initiatives reflecting, it appears, the re-emergence of interest in the therapeutic milieu. Such efforts have though lacked a comprehensive explanation of how organizational culture plays a role in the development of the excessive use of restraint, which seems to respond to such initiatives.

New evidence or changing population? Reviewing the evidence of a link between mental illness and violence.

There has been an apparent shift in majority opinion within psychiatry over the last 20 years on the nature of the relationship between mental illness and violence. Where once there was perhaps widespread scepticism, research, while sometimes producing conflicting results, appears ultimately to have led to the emergence of an almost universal consensus that there is a link. This paper will review the nature of the evidence for such a link between mental illness and violence and explore some of the newer suggestions about why mental illness may sometimes be related to violence.