Cotinine influences the effect of high and low nicotine concentrations on planarian motility differently.

Previous work from our laboratory showed that cotinine, a nicotine metabolite, reverses three nicotine-induced behavioral effects in freshwater planarians: motility decrease, seizure-like movements, and withdrawal-like behaviors. The present work explored whether cotinine, a nicotine metabolite, antagonized the nicotine-induced effects on planarian motility in a concentration-dependent manner. We found that nicotine decreased planarian motility at nicotine concentrations above 60 µM but increased planarian velocity at concentrations equal to or below 50 µM, in agreement with previous data. Cotinine did not affect planarian motility at a concentration range between 250 and 2750 µM. Furthermore, we found that cotinine alleviated the 100 µM nicotine-induced motility decrease in a concentration-dependent manner and reversed the low nicotine concentration motility increase, albeit in a concentration-independent manner. The apparent concentration-dependent alleviation of >60 µM nicotine-induced motility decrease by cotinine suggests an orthosteric relationship between nicotine and cotinine. On the other hand, the evident concentration-independent cotinine alleviation of the increase in motility induced by 50 µM nicotine suggests an allosteric relationship. Our data is consistent with the existing literature about the relationship between nicotine and cotinine in various models, reinforcing the case for the usefulness of the planarian model in pharmacological studies.

Training as imagined? A critical realist analysis of Scotland's internal medicine simulation programme.

BACKGROUND: Evaluating the impact of simulation-based education (SBE) has prioritised demonstrating a causal link to improved patient outcomes. Recent calls herald a move away from looking for causation to understanding 'what else happened'. Inspired by Shorrock's varieties of human work from patient safety literature, this study draws on the concept of work-as-done versus work-as-imagined. Applying this to SBE recognises that some training impacts will be unexpected, and the realities of training will never be quite as imagined. This study takes a critical realist stance to explore the experience and consequences, intended and unintended, of the internal medicine training (IMT) simulation programme in Scotland, to better understand 'training-as-done'. METHODS: Critical realism accepts that there is a reality to uncover but acknowledges that our knowledge of reality is inevitably our construction and cannot be truly objective. The IMT simulation programme involves three courses over a 3-year period: a 3-day boot camp, a skills day and a 2-day registrar-ready course. Following ethical approval, interviews were conducted with trainees who had completed all courses, as well as faculty and stakeholders both immersed in and distant from course delivery. Interviews were audio-recorded, transcribed verbatim and analysed using critical realist analysis, influenced by Shorrock's proxies for work-as-done. RESULTS: Between July and December 2023, 24 interviews were conducted with ten trainees, eight faculty members and six stakeholders. Data described proxies for training-as-done within three broad categories: design, experience and impact. Proxies for training design included training-as-prescribed, training-as-desired and training-as-prioritised which compete to produce training-as-standardised. Experience included training-as-anticipated with pre-simulation anxiety and training-as-unintended with the valued opportunity for social comparison as well as a sense of identity and social cohesion. The impact reached beyond the individual trainee with faculty development and inspiration for other training ventures. CONCLUSION: Our findings highlight unintended consequences of SBE such as social comparison and feeling 'valued as a trainee, valued as a person'. It sheds light on the fear of simulation, reinforcing the importance of psychological safety. A critical realist approach illuminated the 'bigger picture', revealing insights and underlying mechanisms that allow this study to present a new framework for conceptualising training evaluation.

Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

Feasibility and Safety of Oral Risperidone to Treat Prehospital Agitation.

OBJECTIVE: Agitation is a common prehospital problem and frequently presents without a clear etiology. Given the dynamic environment of the prehospital setting, there has historically been a varied approach to treating agitation with a heavy reliance on parenteral medications. Newer best practice guidelines recommend the incorporation of oral medications to treat patients experiencing agitation. Therefore, we evaluated the use of oral risperidone in a single system after a change in protocol occurred. METHODS: This was conducted as a retrospective chart review of an urban/suburban Emergency Medical Services system over the period of 8 months. The first day this medication was implemented throughout the service was included. Charts were included for selection if they included risperidone oral dissolving tablet (ODT) as a charted medication. The primary outcome was administration of additional medications to treat agitation. Exploratory outcome measures included acceptance of medication, documented injury to paramedics, documented injuries to patients, scene times, and adverse events that could possibly be linked to the medication. RESULTS: A total of 552 records were screened for inclusion. Risperidone was offered to 530 patients and accepted by 512 (96.6%). Of these 512 patients, the median age of included patients was 39 years old (IQR 29-52 years old) with a range of 18-89 years old. Rescue or additional medications for agitation were required in 9 (1.8%) cases. There were a total of 4 (0.8%) potential complications following administration of risperidone. There were no reported assaults with subsequent injuries to prehospital personnel or injuries sustained by patients reported in this study. CONCLUSIONS: Risperidone ODT was found to be a safe and effective medication to treat mild agitation in a large urban and suburban EMS system. The need for additional medications to treat agitation was rare, and there were no documented injuries to either patients or paramedics.

The land degradation and desertification-socioeconomic nexus in Egypt's delta region: A case study on Alexandria and Beheira.

The Nile Delta is Egypt's primary source of agricultural production. However, the Delta's capacity to remain Egypt's vital source of food security, rural development and economic stability is diminishing amidst persistent climate change risks. In this regard, this research gauges the impacts of climatic and anthropogenic factors on agricultural revenues and household wealth in Alexandria and Beheira, two of the Delta's most climate-vulnerable governorates. The research employs the Ricardian model by applying Seemingly Unrelated Regressions (SUR), to test the impacts of climate change on real revenues from agriculture. Results show that quadratic temperature negatively impacts revenues from agriculture in Alexandria, while employment in agriculture, irrigation, livestock and machines positively contribute to revenues. In Beheira, results show that temperature and machines negatively contribute to agricultural revenues, while livestock contributes positively. The research further estimates the socioeconomic impacts of land degradation and desertification on individuals in Alexandria and Beheira by using Ordinary Least Squares (OLS) robust standard errors. Individuals' socio-economic status, proxied by their wealth index (WI), is regressed on the Environmental Sensitivity Index (ESI), gender, age, education, household size, work in agriculture and rural/urban residence. Outcomes reveal that individuals' wealth status in Alexandria is positively correlated with ESI, age, and education. In Beheira, land degradation, household size, rural areas and fathers working in agriculture are negatively correlated with wealth. Education, however, contributes positively to wealth. The study proposes policy implications that aim to foster the growth and development of rural residents in the Delta region.

Effect of a person-centred goals-of-care form and clinical communication training on shared decision-making and outcomes in an acute hospital: a prospective longitudinal interventional study.

BACKGROUND: Patients with a life-limiting illness (LLI) requiring hospitalisation have a high likelihood of deterioration and 12-month mortality. To avoid non-aligned care, we need to understand our patients' goals and values. AIM: To describe the association between the implementation of a shared decision-making (SDM) programme and documentation of goals of care (GoC) for hospitalised patients with LLI. METHODS: A prospective longitudinal interventional study of patients admitted to acute general medicine wards in an Australian tertiary hospital over 5 years was conducted. A SDM programme with a new GoC form, communication training and clinical support was implemented. The primary outcome was the proportion of patients with a documented person-centred GoC discussion (PCD). Clinical outcomes included hospital utilisation and 90-day mortality. RESULTS: 1343 patients were included. The proportion of patients with PCDs increased from 0% to 35.4% (adjusted odds ratio (aOR), 2.38; 95% confidence interval (CI), 2.01-2.82; P < 0.001). During this time, median hospital length of stay decreased from 8 days (interquartile range (IQR), 4-14) to 6 days (IQR, 3-11) (adjusted estimate effect, -0.38; 95% CI, -0.64 to -0.11; P = 0.005) and rapid response team activation from 28% to 13% (aOR, 0.87; 95% CI, 0.78-0.97; P value = 0.01). Documented treatment preference of high-dependency unit care decreased from 39.7% to 24.4% (aOR, 0.81; 95% CI, 0.73-0.89; P value < 0.001), and ward-based care increased from 31.9% to 55.1% (aOR, 1.24; 95% CI, 1.14-1.36; P value < 0.001). CONCLUSION: The implementation of a SDM programme was associated with increased documentation of person-centred GoC, changed patient treatment preference to lower intensity care and reduced hospital utilisation.

Implementation of Extracorporeal CPR Programs for Out-of-Hospital Cardiac Arrest: Another Tale of Two County Hospitals.

Extracorporeal cardiopulmonary resuscitation (ECPR) is a form of intensive life support that has seen increasing use globally to improve outcomes for patients who experience out-of-hospital cardiac arrest (OHCA). Hospitals with advanced critical care capabilities may be interested in launching an ECPR program to offer this support to the patients they serve; however, to do so, they must first consider the significant investment of resources necessary to start and sustain the program. The existing literature describes many single-center ECPR programs and often focuses on inpatient care and patient outcomes in hospitals with cardiac surgery capabilities. However, building a successful ECPR program and using this technology to support an individual patient experiencing refractory cardiac arrest secondary to a shockable rhythm depends on efficient out-of-hospital and emergency department (ED) management. This article describes the process of implementing 2 intensivist-led ECPR programs with limited cardiac surgery capability. We focus on emergency medical services and ED clinician roles in identifying patients, mobilizing resources, initiation and management of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the ED, and ongoing efforts to improve ECPR program quality. Each center experienced a significant learning curve to reach goals of arrest-to-flow times of cannulation for ECPR. Building consensus from multidisciplinary stakeholders, including out-of-hospital stakeholders; establishing shared expectations of ECPR outcomes; and ensuring adequate resource support for ECPR activation were all key lessons in improving our ECPR programs.

A Practical Solution for Preoxygenation in the Prehospital Setting: A Nonrebreather Mask with Flush Rate Oxygen.

OBJECTIVE: Prehospital clinicians need a practical means of providing adequate preoxygenation prior to intubation. A bag-valve-mask (BVM) can be used for preoxygenation in perfect conditions but is likely to fail in emergency settings. For this reason, many airway experts have moved away from using BVM for preoxygenation and instead suggest using a nonrebreather (NRB) mask with flush rate oxygen.Literature on preoxygenation has suggested that a NRB mask delivering flush rate oxygen (on a 15 L/min O2 regulator, maximum flow, ∼50 L/min) is noninferior to BVM at 15 L/min held with a tight seal. However, in the prehospital setting, where emergency airway management success varies, preoxygenation techniques have not been deeply explored. Our study seeks to determine whether preoxygenation can be optimally performed with NRB at flush rate oxygen. METHODS: We performed a crossover trial using healthy volunteers. Subjects underwent 3-min trials of preoxygenation with NRB mask at 25 L/min oxygen delivered from a portable tank, NRB at flush rate oxygen from a portable tank, NRB with flush rate oxygen from an onboard ambulance tank, and BVM with flush rate oxygen from an onboard ambulance tank. The primary outcome was the fraction of expired oxygen (FeO2). We compared the FeO2 of the BVM-flush to other study groups, using a noninferiority margin of 10%. RESULTS: We enrolled 30 subjects. Mean FeO2 values for NRB-25, NRB-flush ambulance, NRB-flush portable, and BVM-flush were 63% (95% confidence interval [CI] 58-68%), 74% (95%, CI 70-78%), 78% (95%, CI 74-83%), and 80% (95%, CI 75-84%), respectively. FeO2 values for NRB-flush on both portable tank and ambulance oxygen were noninferior to BVM-flush on the ambulance oxygen system (FeO2 differences of 1%, 95% CI -3% to 6%; and 6%, 95% CI 1-10%). FeO2 for the NRB-25 group was inferior to BVM-flush (FeO2 difference 16%, 95% CI 12-21%). CONCLUSIONS: Among healthy volunteers, flush rate preoxygenation using NRB masks is noninferior to BVM using either a portable oxygen tank or ambulance oxygen. This is significant because preoxygenation using NRB masks with flush rate oxygen presents a simpler alternative to the use of BVMs. Preoxygenation using NRB masks at 25 L/min from a portable tank is inferior to BVM at flush rate.

Enhancement of Metal Nanostructure Deposition on Silicon Laser-Induced Periodic Surface Structures by Galvanic Replacement.

We report a chemically motivated, single-step method to enhance metal deposition onto silicon laser-induced periodic surface structures (LIPSSs) using reactive laser ablation in liquid (RLAL). Galvanic replacement (GR) reactions were used in conjunction with RLAL (GR-RLAL) to promote the deposition of Au and Cu nanostructures onto a Si LIPSS. To increase the deposition of Au, sacrificial metals Cu, Fe, and Zn were used; Fe and Zn also enhanced the deposition of Cu. We show that the deposited metal content, surface morphology, and metal crystallite size can be tuned based on the difference in electrochemical potentials of the deposited and sacrificial metal. Compared to the Au and Cu reference samples, GR more than doubled the metal content on the LIPSS and reduced metal crystallite sizes by up to 20%. The ability to tune the metal content and crystalline domain size simultaneously makes GR-RLAL a potentially useful approach in the manufacturing of functional metal-LIPSS materials such as surface-enhanced Raman spectroscopy substrates.

Effect of communication skills training on documentation of shared decision-making for patients with life-limiting illness: An observational study in an intensive care unit.

Objectives: This article aims to examine the association between a shared decision-making (SDM) clinical communication training program and documentation of SDM for patients with life-limiting illness (LLI) admitted to intensive care. Methods: This article used a prospective, longitudinal observational study in a tertiary intensive care unit (ICU). Outcomes included the proportion of patients with SDM documented on an institutional Goals of Care Form during hospital admission, as well as characteristics, outcomes, and factors associated with an SDM admission. Intervention: Clinical communication skills training (iValidate) and clinical support program are the intervention for this study. Results: A total of 325 patients with LLI were admitted to the ICU and included in the study. Overall, 184 (57%) had an SDM admission, with 79% of Goals of Care Form completed by an iValidate-trained doctor. Exposure to an iValidate-trained doctor was the strongest predictor of an ICU patient with LLI having an SDM admission (odds ratio: 22.72, 95% confidence interval: 11.91-43.54, p < 0.0001). A higher proportion of patients with an SDM admission selected high-dependency unit-level care (29% vs. 12%, p < 0.001) and ward-based care (36% vs. 5%, p < 0.0001), with no difference in the proportion of patients choosing intensive care or palliative care. The proportion of patients with no deterioration plan was higher in the non-SDM admission cohort (59% vs. 0%, p < 0.0001). Conclusions: Clinical communication training that explicitly teaches identification of patient values is associated with improved documentation of SDM for critically ill patients with LLI. Understanding the relationship between improved SDM and patient, family, and clinical outcomes requires appropriately designed high-quality trials randomised at the patient or cluster level.

Supraglottic airway devices are associated with asphyxial physiology after prolonged CPR in patients with refractory Out-of-Hospital cardiac arrest presenting for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Multiple randomized clinical trials have compared specific airway management strategies during ACLS with conflicting results. However, patients with refractory cardiac arrest died in almost all cases without the availability of extracorporeal cardiopulmonary resuscitation (ECPR). Our aim was to determine if endotracheal intubation (ETI) was associated with improved outcomes compared to supraglottic airways (SGA) in patients with refractory cardiac arrest presenting for ECPR. METHODS: We retrospectively studied 420 consecutive adult patients with refractory out-of-hospital cardiac arrest due to shockable presenting rhythms presenting to the University of Minnesota ECPR program. We compared outcomes between patients receiving ETI (n = 179) and SGA (n = 204). The primary outcome was the pre-cannulation arterial PaO2 upon arrival to the ECMO cannulation center. Secondary outcomes included neurologically favorable survival to hospital discharge and eligibility for VA-ECMO based upon resuscitation continuation criteria applied upon arrival to the ECMO cannulation center. RESULTS: Patients receiving ETI had significantly higher median PaO2 (71 vs. 58 mmHg, p = 0.001), lower median PaCO2 (55 vs. 75 mmHg, p < 0.001), and higher median pH (7.03 vs. 6.93, p < 0.001) compared to those receiving SGA. Patients receiving ETI were also significantly more likely to meet VA-ECMO eligibility criteria (85% vs. 74%, p = 0.008). Of patients eligible for VA-ECMO, patients receiving ETI had significantly higher neurologically favorable survival compared to SGA (42% vs. 29%, p = 0.02). CONCLUSIONS: ETI was associated with improved oxygenation and ventilation after prolonged CPR. This resulted in increased rate of candidacy for ECPR and increased neurologically favorable survival to discharge with ETI compared to SGA.

Climate-resilient development planning for cities: progress from Cape Town.

Priorities and programmes in the City of Cape Town's Integrated Development Plan (2022-2027) demonstrate progress towards operationalising local level planning for climate-resilient development. These developments provide lessons of process and focus on transformative outcomes for cities seeking equitable and just development while implementing climate change adaptation and mitigation.

Adaptation to compound climate risks: A systematic global stocktake.

This article provides a stocktake of the adaptation literature between 2013 and 2019 to better understand how adaptation responses affect risk under the particularly challenging conditions of compound climate events. Across 39 countries, 45 response types to compound hazards display anticipatory (9%), reactive (33%), and maladaptive (41%) characteristics, as well as hard (18%) and soft (68%) limits to adaptation. Low income, food insecurity, and access to institutional resources and finance are the most prominent of 23 vulnerabilities observed to negatively affect responses. Risk for food security, health, livelihoods, and economic outputs are commonly associated risks driving responses. Narrow geographical and sectoral foci of the literature highlight important conceptual, sectoral, and geographic areas for future research to better understand the way responses shape risk. When responses are integrated within climate risk assessment and management, there is greater potential to advance the urgency of response and safeguards for the most vulnerable.

Implementation of Extracorporeal Membrane Oxygenation Without On-Site Cardiac Surgery or Perfusion Support: A Tale of Two County Hospitals.

Patients with refractory respiratory and cardiac failure may present to noncardiac surgery centers. Prior studies have demonstrated that acute care surgeons, intensivists, and emergency medicine physicians can safely cannulate and manage patients receiving extracorporeal membrane oxygenation (ECMO). Harborview Medical Center (Harborview) and Hennepin County Medical Center (Hennepin) are both urban, county-owned, level 1 trauma centers that implemented ECMO without direct, on-site cardiac surgery or perfusion support. Both centers 1) use an ECMO specialist model staffed by specially trained nurses and respiratory therapists and 2) developed comparable training curricula for ECMO specialists, intensivists, surgeons, and trainees. Each program began with venovenous ECMO to provide support for refractory hypoxemic respiratory failure and subsequently expanded to venoarterial ECMO support. The coronavirus disease 2019 (COVID-19) pandemic created an impetus for restructuring, with each program creating a consulting service to facilitate ECMO delivery across multiple intensive care units (ICUs) and to promote fellow and resident training and experience. Both Harborview and Hennepin, urban county hospitals 1,700 miles apart in the United States, independently implemented and operate adult ECMO programs without involvement from cardiovascular surgery or perfusion services. This experience further supports the role of ECMO specialists in the delivery of extracorporeal life support.

Integrating climate change in Environmental Impact Assessment: A review of requirements across 19 EIA regimes.

The contribution of human activities to climate change is well understood. Yet the integration of climate change considerations into local decision making tools designed to govern activities affecting the environment, such as Environmental Impact Assessments (EIAs), remains underdeveloped and inconsistently applied for proposed policies, programs, plans and projects. This study reviews progress across a range of 19 EIA regimes and identifies and assesses regulations and guidelines that have been established to promote the integration of climate change considerations within EIAs. A typology of levels of integration is developed to guide analysis across multiple EIA regimes. The findings identify a global and growing requirement for climate change aspects to be considered within EIAs and describe the range of ways this is done across the regimes selected. Climate change is typically concerned with the mitigation of greenhouse gas emissions from proposed developments in EIAs. Fewer regimes are concerned with climate change adaptation, and in general, an integration deficit is identified for regimes where climate change is only partially considered. Examples of high integration indicate that EIA holds the potential to play a substantive role in climate change governance at project level decision making, suggesting the tools hold promise for local level climate governance. However, many domestic obstacles can militate against integration, including political, socio-technical, and economic imperatives, particularly for exemptions of sector and scope. Nevertheless, examples also indicate advances can be made through jurisprudence during the EIA review stage to establish new precedents of how climate should be considered in EIAs. Potential future research and practice directions are identified, and recommendations include the development of regulations and practice guidelines; inclusion of climate change adaptation; strengthening post-decision monitoring; application to all relevant sectors and activities; alignment with SEA; and integration across all stages of the EIA process.

Extracorporeal membrane oxygenation versus conventional rewarming for severe hypothermia in an urban emergency department.

BACKGROUND: Severe hypothermia (core body temperature < 28°C) is life-threatening and predisposes to cardiac arrest. The comparative effectiveness of different active internal rewarming methods in an urban U.S. population is unknown. We aim to compare outcomes between hypothermic emergency department (ED) patients rewarmed conventionally using an intravascular rewarming catheter or warm fluid lavage versus those rewarmed using extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective cohort analysis of adults with severe hypothermia due to outdoor exposure presenting to an urban ED in Minnesota, 2007-2021. The primary outcome was hospital survival. We also calculated the rewarming rate in the 4 h after ED arrival and compared these data between patients rewarmed with ECMO (the extracorporeal rewarming group) versus without ECMO (the conventional rewarming group). We repeated these analyses in the subgroup of patients with cardiac arrest. RESULTS: We analyzed 44 hypothermic ED patients: 25 patients in the extracorporeal rewarming group (median temperature 24.1°C, 84% with cardiac arrest) and 19 patients in the conventional rewarming group (median temperature 26.3°C, 37% with cardiac arrest; 89% received an intravascular rewarming catheter). The median rewarming rate was greater in the extracorporeal versus conventional group (2.3°C/h vs. 1.5°C/h, absolute difference 0.8°C/h, 95% confidence interval [CI] 0.3-1.2°C/h) yet hospital survival was similar (68% vs. 74%). Among patients with cardiac arrest, hospital survival was greater in the extracorporeal versus conventional group (71% vs. 29%, absolute difference 42%, 95% CI 4%-82%). CONCLUSIONS: Among ED patients with severe hypothermia and cardiac arrest, survival was significantly higher with ECMO versus conventional rewarming. Among all hypothermic patients, ECMO use was associated with faster rewarming than conventional methods.

Prehospital Ultrasound Diagnosis of Massive Pulmonary Embolism by Non-Physicians: A Case Series.

Massive pulmonary embolism (hemodynamically unstable, defined as systolic BP <90 mmHg) has significant morbidity and mortality. Point of care ultrasound (POCUS) has allowed clinicians to detect evidence of massive pulmonary embolism much earlier in the patient's clinical course, especially when patient instability precludes computerized tomography confirmation. POCUS detection of massive pulmonary embolism has traditionally been performed by physicians. This case series demonstrates four cases of massive pulmonary embolism diagnosed with POCUS performed by non-physician prehospital personnel.

Traffic-generated air pollution - Exposure mediated expression of factors associated with demyelination in a female apolipoprotein E-/- mouse model.

Epidemiology studies suggest that exposure to ambient air pollution is associated with demyelinating diseases in the central nervous system (CNS), including multiple sclerosis (MS). The pathophysiology of MS results from an autoimmune response involving increased inflammation and demyelination in the CNS, which is higher in young (adult) females. Exposure to traffic-generated air pollution is associated with neuroinflammation and other detrimental outcomes in the CNS; however, its role in the progression of pathologies associated with demyelinating diseases has not yet been fully characterized in a female model. Thus, we investigated the effects of inhalation exposure to mixed vehicle emissions (MVE) in the brains of both ovary-intact (ov+) and ovariectomized (ov-) female Apolipoprotein (ApoE-/-) mice. Ov + and ov- ApoE-/- mice were exposed via whole-body inhalation to either filtered air (FA, controls) or mixed gasoline and diesel vehicle emissions (MVE: 200 PM µg/m3) for 6 h/d, 7 d/wk., for 30 d. We then analyzed MVE-exposure mediated alterations in myelination, the presence of CD4+ and CD8+ T cells, reactive oxygen species (ROS), myelin oligodendrocyte protein (MOG), and expression of estrogen (ERα and ERß) and progesterone (PROA/B) receptors in the CNS. MVE-exposure mediated significant alterations in myelination across multiple regions in the cerebrum, as well as increased CD4+ and CD8+ staining. There was also an increase in ROS production in the CNS of MVE-exposed ov- and ov + ApoE-/- mice. Ov- mice displayed a reduction in cerebral ERα mRNA expression, compared to ov + mice; however, MVE exposure resulted in an even further decrease in ERα expression, while ERß and PRO A/B were unchanged across groups. These findings collectively suggest that inhaled MVE-exposure may mediate estrogen receptor expression alterations associated with increased CD4+/CD8+ infiltration, regional demyelination, and ROS production in the CNS of female ApoE-/- mice.