Health and Environmental Effects Document on Geothermal Energy -- 1982 update

We assess several of the important health and environmental risks associated with a reference geothermal industry that produces 21,000 MWe for 30 y (equivalent to 20 x 10{sup 18} J). The analyses of health effects focus on the risks associated with exposure to hydrogen sulfide, particulate sulfate, benzene, mercury, and radon in air and arsenic in food. Results indicate that emissions of hydrogen sulfide are likely to cause odor-related problems in 29 of 51 geothermal resources areas, assuming that no pollution controls are employed. Our best estimates and ranges of uncertainty for the health risks of chronic population exposures to atmospheric pollutants are as follows (risks expressed per 10{sup 18} J of electricity): particulate sulfate, 44 premature deaths (uncertainty range of 0 to 360); benzene, 0.15 leukemias (range of 0 to 0.51); elemental mercury, 14 muscle tremors (range of 0 to 39); and radon, 0.68 lung cancers (range of 0 to 1.8). The ultimate risk of fatal skin cancers as the result of the transfer of waste arsenic to the general population over geologic time ({approx} 100,000 y) was calculated as 41 per 10{sup 18} J. We based our estimates of occupational health effects on rates of accidental deaths together with data on occupational diseases and injuries in surrogate industries. According to our best estimates, there would be 8 accidental deaths per 10{sup 18} J of electricity, 300 cases of occupational diseases per 10{sup 18} J, and 3400 occupational injuries per 10{sup 18}J. The analysis of the effects of noncondensing gases on vegetation showed that ambient concentrations of hydrogen sulfide and carbon dioxide are more likely to enhance rather than inhibit the growth of plants. We also studied the possible consequences of accidental releases of geothermal fluids and concluded that probably less than 5 ha of land would be affected by such releases during the production of 20 x 10{sup 18} J of electricity. Boron emitted from cooling towers in the Imperial Valley was identified as a potential source of crop damage. Our analyses, however, showed that such damage is unlikely. Finally, we examined the nonpollutant effects of land subsidence and induced seismicity. Land subsidence is possible around some facilities, but surface-related damage is not expected to be great. Induced seismic events that have occurred to date at geothermal resource areas have been nondestructive. It is not possible to predict accurately the risk of potentially destructive events, and more research is needed in this area

Neuroinflammation and the Glial Response Contribute to Both Beneficial and Pathological Outcomes in Multiple Disease Models

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Pathology and Laboratory Medicine, 2015.Neuroinflammation has been considered a driver of pathology and cognitive dysfunction for many years; however, not all inflammation results in the same outcome. The brain is sensitive to a wide variety of inflammatory stimuli that can result in different outcomes depending on the type of exposure, environment, and underlying pathological processes. In order to gain a better understanding of the relationship between neuroinflammation and brain pathology, we developed three models comprising unique inflammatory stimuli. The first model aimed to understand how peripheral inflammation contributes to neuroinflammation. To accomplish this, a 10% total body area full thickness thermal burn was used to induce significant peripheral inflammation without lethality. Prior to burn injury, mice were subjected to 0 or 5 Gy whole body gamma radiation. Typically, only doses over 15 Gy are sufficient to induce neuroinflammation, so a possible combinative effect of combination injury was investigated. Mice were followed out to 6 hours, 1 week, or 6 months. Combination injury resulted in a significant elevation of mRNA for both the vascular marker ICAM-1 and the inflammatory marker TNFα at 6 hours. Interestingly, combination injury also showed increased IL-6 serum protein levels suggesting elevated peripheral inflammation as well. Furthermore, enhanced glial cell activation by CD68 and Iba1 immunohistochemistry was seen at all time points for the combination injury. Lastly, combination injury lead to significant learning and memory deficits compared to the single injuries alone, suggesting a functional synergy between peripheral inflammation arising from burn and brain radiation injury. In addition to cognitive dysfunction, neuroinflammation has been posited to be a driver of pathology in many diseases. One prominent case is Alzheimer’s disease (AD). To explore this relationship, the APP/PS1 AD mouse model was subjected to 0, 10, or 100 cGy 56Fe particle galactic cosmic radiation (GCR). Six months after exposure, irradiated mice showed decreased cognitive abilities. Interestingly, in male mice we observed acceleration of Aβ plaque pathology using Congo red and 6E10 staining, which was confirmed via ELISA. No microglial activation was observed at this time point, but elevated ICAM-1 levels were seen, suggesting a potential vascular mechanism. These two studies suggest that neuroinflammation is a detrimental process leading to cognitive dysfunction and pathology. However, neuroinflammation is a normal response to injury that likely has protective functions. Interestingly, several studies have demonstrated that blocking neuroinflammation does not always mitigate pathology, and in some cases, enhances it. This suggests a more complex nature to neuroinflammation than previously thought. The last model explored these seeming paradoxical findings that in some cases, neuroinflammation can result in amelioration of pathology. Using an adeno-associated viral vector carrying a human IL-1β cDNA to transduce mice, neuroinflammation was induced in one hippocampus of 8-month-old APP/PS1 mice for 4 weeks, while the other hemisphere received a control viral injection. We observed a robust activation of alternatively activated, anti-inflammatory (M2) microglia using the marker Arg1. This increase in Arg1+ microglia coincided with a reduction in Aβ plaques. Arg1+ microglia were shown to contain Aβ suggesting they were the mechanism of clearance. When IL-4 was used to specifically induce Arg1+ microglia, there was significant plaque reduction. Conversely, blocking induction of Arg1+ microglia during chronic inflammation impaired plaque clearance. Together these findings demonstrate that Arg1+ microglia are necessary and sufficient for Aβ plaque reduction during neuroinflammation. Overall, these three models of neuroinflammation provide a better understanding of how inflammation influences both cognitive function and disease progression. Furthermore, they can guide us towards possible avenues for immunomodulatory therapy of brain disorders

Adult murine hippocampal neurogenesis is inhibited by sustained IL-1 beta and not rescued by voluntary running

Acute neuroinflammation reduces adult hippocampal neurogenesis but the role of chronic neuroinflammation, which may be more representative of ongoing processes in CNS disorders, remains relatively unknown. Interleukin-1 beta (IL-1 beta) is a pro-inflammatory cytokine that has been shown to acutely impair neurogenesis. To further investigate the relationship between sustained 1L-1 beta expression and adult neurogenesis, a mouse model with an IL-1 beta excisionally activated transgene, IL-1 beta(XAT) was utilized. Upon exposure to Cre recombinase, IL-1 beta overexpression in this model results in chronic neuroinflammation, which persists up to 12 months and causes glial activation, cellular recruitment, and deficits in learning and memory. We hypothesized that adult neurogenesis would be reduced by sustained hippocampal IL-1 beta overexpression and rescued by voluntary running, which has been shown to enhance neurogenesis. Hippocampal inflammation in the IL-1 beta(XAT) model severely impaired doublecortin (DCX) positive cells at 1 and 3 months after IL-1 beta induction. Furthermore, BrdU labeling demonstrated a shift in cell lineage from neuronal to astroglial in the context of sustained hippocampal IL-1 beta overexpression. Deletion of the IL-1 receptor prevented the decrease in DCX+ cells. Voluntary running did not attenuate the effects of IL-1 beta expression demonstrated by DCX staining. These results suggest that chronic neuroinflammation severely impairs adult hippocampal neurogenesis and voluntary running is not beneficial as a therapy to rescue these effects. (C) 2011 Elsevier Inc. All rights reserved

Targeting innate immunity for neurodegenerative disorders of the central nervous system

Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article.</p

Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

BACKGROUND: Patients undergoing surgery with perioperative COVID-19 are suggested to have worse outcomes, but whether this is COVID-related or due to selection bias remains unclear. We aimed to compare the postoperative outcomes of patients with and without perioperative COVID-19. METHODS: Patients with perioperative COVID-19 diagnosed within 7 days before or 30 days after surgery between February and July 2020 from 68 US hospitals in COVIDSurg, an international multicenter database, were 1:1 propensity score matched to patients without COVID-19 undergoing similar procedures in the 2012 American College of Surgeons National Surgical Quality Improvement Program database. The matching criteria included demographics (e.g., age, sex), comorbidities (e.g., diabetes, chronic obstructive pulmonary disease, chronic kidney disease), and operation characteristics (e.g., type, urgency, complexity). The primary outcome was 30-day hospital mortality. Secondary outcomes included hospital length of stay and 13 postoperative complications (e.g., pneumonia, renal failure, surgical site infection). RESULTS: A total of 97,936 patients were included, 1,054 with and 96,882 without COVID-19. Prematching, COVID-19 patients more often underwent emergency surgery (76.1% vs. 10.3%, p &lt; 0.001). A total of 843 COVID-19 and 843 non-COVID-19 patients were successfully matched based on demographics, comorbidities, and operative characteristics. Postmatching, COVID-19 patients had a higher mortality (12.0% vs. 8.1%, p = 0.007), longer length of stay (6 [2-15] vs. 5 [1-12] days), and higher rates of acute renal failure (19.3% vs. 3.0%, p &lt; 0.001), sepsis (13.5% vs. 9.0%, p = 0.003), and septic shock (11.8% vs. 6.0%, p &lt; 0.001). They also had higher rates of thromboembolic complications such as deep vein thrombosis (4.4% vs. 1.5%, p &lt; 0.001) and pulmonary embolism (2.5% vs. 0.4%, p &lt; 0.001) but lower rates of bleeding (11.6% vs. 26.1%, p &lt; 0.001). CONCLUSION: Patients undergoing surgery with perioperative COVID-19 have higher rates of 30-day mortality and postoperative complications, especially thromboembolic, compared with similar patients without COVID-19 undergoing similar surgeries. Such information is crucial for the complex surgical decision making and counseling of these patients. (J Trauma Acute Care Surg. 2023;94: 513-524. Copyright (C) 2023 American Association for the Surgery of Trauma.)LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV

Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA. A Prospective Multicenter Study

Objective: To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Background: Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists. Methods: As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results: A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions: Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks