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Introduction:  Student-run free clinics (SRFCs) are a recent popular addition to medical school education, and a subset of studies has looked at the influence of SRFC volunteering on the medical student's career development. The majority of the research done in this area has focused on understanding if these SRFCs produce physicians who are more likely to practice medicine in underserved communities, caring for the uninsured. The remainder of the research has investigated if volunteering in an SRFC influences the specialty choice of medical school students. The results of these specialty choice studies give no definitive answer as to whether medical students chose primary or specialty care residencies as a result of their SRFC experience. Keeping Neighbors in Good Health through Service (KNIGHTS) is the SRFC of the University of Central Florida College of Medicine (UCF COM). Both primary and specialty care is offered at the clinic. It is the goal of this study to determine if volunteering in the KNIGHTS SRFC influences UCF COM medical students to choose primary care, thereby helping to meet the rising need for primary care physicians in the United States., Methods:  A survey was distributed to first, second, and third-year medical students at the UCF COM to collect data on demographics, prior volunteering experience, and specialty choice for residency. Responses were then combined with records of volunteer hours from the KNIGHTS Clinic and analyzed for correlations. We analyzed the frequency and Pearson's chi-squared values. A p value of less than 0.05 was considered statistically significant., Results:  Our survey had a total response rate of 39.8%. We found that neither the act of becoming a KNIGHTS Clinic volunteer nor the hours volunteered at the KNIGHTS Clinic influenced the UCF COM student's choice to enter a primary care specialty (p = NS). Additionally, prior volunteering/clinical experience or the gender of the medical school student did not influence a student's choice to volunteer at the KNIGHTS Clinic., Discussion:  Volunteering at KNIGHTS Clinic did not increase student choice to enter primary care, with students choosing other specialties at equal rates, probably due to the variety of specialties present at the KNIGHTS Clinic. This suggests that the volunteer attending physicians present at an SRFC may influence the choice of residency for students. It also suggests that SFRCs are not a viable tool to increase the number of primary care doctors in the United States., Competing Interests: The authors have declared that no competing interests exist.

Background: Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results: In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions: This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure. [ABSTRACT FROM AUTHOR]

Current evidence shows inconsistencies about ambient air pollution (AAP) exposure as a risk factor for Parkinson's disease (PD). We performed meta-analyses to estimate the pooled risk of PD due to AAP exposure. We performed a systematic search in PubMed, Google Scholar, The Cochrane Library, and J-GATEPLUS databases for peer-reviewed epidemiological studies reporting the risk of PD due to exposure to PM2.5, PM10, O3, CO, NO2, NOX and SO2; from the beginning until October 2021. The pooled odds ratio (OR) for the effect of NO2 (per 1 μg/m3) and O3 (per 1 ppb) on PD was 1.01[95% CI: 1.00,1.02; I2 = 69% (p =.01)] and 1.01 [95% CI: 1.00,1.02; I2 = 66% (p =.03)], respectively. The ORs for the effects of PM2.5 (per 1 µg/m3) and CO (per 1 ppm) on PD were 1.01 [95% CI:.99,1.03; I2 = 40%] and 1.64 [95% CI:.96,2.78; I2 = 75% (p =.01)], respectively. The study showed the adverse roles of NO2, O3, PM2.5, and CO in increasing the risk for PD. [ABSTRACT FROM AUTHOR]

Exposure to traffic-related air pollution consisting of particulate matter (PM) is associated with cognitive decline leading to Alzheimer's disease (AD). In this study, we sought to examine the neurotoxic effects of exposure to ultrafine PM and how it exacerbates neuronal loss and AD-like neuropathology in wildtype (WT) mice and a knock-in mouse model of AD (AppNL-G-F/+ -KI) when the exposure occurs at a prepathologic stage or at a later age with the presence of neuropathology. AppNL-G-F/+ -KI and WT mice were exposed to concentrated ultrafine PM from local ambient air in Irvine, California, for 12 weeks, starting at 3 or 9 months of age. Particulate matter-exposed animals received concentrated ultrafine PM up to 8 times above the ambient levels, whereas control animals were exposed to purified air. Particulate matter exposure resulted in a marked impairment of memory tasks in prepathologic AppNL-G-F/+ -KI mice without measurable changes in amyloid-β pathology, synaptic degeneration, and neuroinflammation. At aged, both WT and AppNL-G-F/+ -KI mice exposed to PM showed a significant memory impairment along with neuronal loss. In AppNL-G-F/+ -KI mice, we also detected an increased amyloid-β buildup and potentially harmful glial activation including ferritin-positive microglia and C3-positive astrocytes. Such glial activation could promote the cascade of degenerative consequences in the brain. Our results suggest that exposure to PM impairs cognitive function at both ages while exacerbation of AD-related pathology and neuronal loss may depend on the stage of pathology, aging, and/or state of glial activation. Further studies will be required to unveil the neurotoxic role of glial activation activated by PM exposure. [ABSTRACT FROM AUTHOR]

Medical pro bono, in which medical professionals provide no (or low) cost services, is one approach to addressing unmet healthcare needs. Prior efforts to understand who chooses to take part in pro bono and why they might do so have been primarily atheoretical in their approach. The current investigation focuses on students in medical school and draws on relevant theory and research in psychology to identify predictors of their intentions to engage in medical pro bono service during and after medical school. Hypotheses:Four major approaches to identifying predictors of medical pro bono are examined: the role of demographic variables as predictors of medical pro bono, conceptualizing medical pro bono as a form of volunteerism, viewing medical pro bono as an expression of personality, and medical pro bono as a reflection of role identities and expectations. Each of these approaches can be characterized as being about medical students' individual attributes or aspects of the situation they are in. A total of 278 medical students from 15 different medical schools in the United States of America completed a web-based survey (8/4/2020–9/22/2020). The students completed measures of pro bono identity and expectations, intentions to engage in medical pro bono activities, prosocial personality, volunteer motivation, exposure to volunteering, general traits of personality, and demographic variables (in this order). We used linear regression analyses to separately predict three measures of intentions (general medical school intentions, intentions toward medical pro bono trips during medical school, and general post medical school intentions). The strongest predictors of intentions to engage in medical pro bono were one's identity and expectations related to pro bono. Medical students who had incorporated medical pro bono into aspects of their identity and/or considered medical pro bono to be an expectation indicated higher intentions to engage in medical pro bono work. Conversely, volunteer motivation/exposure, personality, and demographic variables were much weaker predictors of medical pro bono. The findings of the present study have implications for ways that medically oriented volunteering may be increased by individual-level interventions and/or changes in medical education. Individual-level interventions could leverage the importance of identity and expectations to craft persuasive messaging to appeal to identity and expectations as drivers of engagement in medical pro bono. Program level interventions could work toward the institutionalization of medical pro bono by the inclusion/promotion of medical pro bono into the program's co-curricular and/or extracurricular activities. [ABSTRACT FROM AUTHOR]

Student-run clinics (SRCs) offer unique opportunities for students to engage in healthcare delivery, but the student learning outcomes of such clinics have not yet been systematically examined in a comprehensive manner. The purpose of this review was to appraise and synthesize existing literature pertaining to student learning outcomes associated with participation in SRCs. A systematic review was undertaken using PubMed, CINAHL, and Web of Science databases. The quality of articles that met inclusion criteria articles was appraised using the Mixed Methods Appraisal Tool (MMAT). Study details, such as learning outcomes, were also extracted. Ninety-two studies met inclusion criteria. Most studies were conducted in North America (n = 73, 79.3%), and related to clinics involving solely medical students (n = 35, 38.0%) or multi-professional clinics (n = 34, 37.0%). Demonstrated learning outcomes of SRC participation include clinical skills, interprofessional skills, empathy/compassion for underserved patients, and leadership. SRC participation had little apparent impact on students' future career directions. Quality appraisal via the MMAT found mixed levels of research quality amongst reviewed studies. In summary, while SRC participation appears to offer benefits for student learning, improved study design and research outside of North American contexts would further advance knowledge. [ABSTRACT FROM AUTHOR]

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity. Objectives: We used an ex vivo system to evaluate the effect of in vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission. Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [3H]-dopamine were assessed in striatal synaptosomes, and dopamine D2 receptor (D2R) affinity for dopamine was evaluated by the displacement of [3H]-spiperone binding to striatal membranes. Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP −25%, UFP −32%; ambulatory time: FP −24%, UFP −22%; ambulatory episodes: FP −22%, UFP −30%), decreased [3H]-dopamine uptake (FP −18%, UFP −24%), and increased, although not significantly, [3H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D2R density or affinity for dopamine. Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders. Young adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days. Exposure to FP or UFP reduced motor activity. Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes. Neither D2R density or affinity for dopamine was affected by FP or UFP. UFP was more potent than FP to exert the effects reported. [ABSTRACT FROM AUTHOR]

The World Health Organization lists air pollution as one of the top five risks for developing chronic non-communicable disease, joining tobacco use, harmful use of alcohol, unhealthy diets and physical inactivity. This review focuses on how host defense mechanisms against adverse airborne exposures relate to the probable interacting and overlapping pathophysiological features of neurodegeneration and multiple chemical sensitivity. Significant long-term airborne exposures can contribute to oxidative stress, systemic inflammation, transient receptor subfamily vanilloid 1 (TRPV1) and subfamily ankyrin 1 (TRPA1) upregulation and sensitization, with impacts on olfactory and trigeminal nerve function, and eventual loss of brain mass. The potential for neurologic dysfunction, including decreased cognition, chronic pain and central sensitization related to airborne contaminants, can be magnified by genetic polymorphisms that result in less effective detoxification. Onset of neurodegenerative disorders is subtle, with early loss of brain mass and loss of sense of smell. Onset of MCS may be gradual following long-term low dose airborne exposures, or acute following a recognizable exposure. Upregulation of chemosensitive TRPV1 and TRPA1 polymodal receptors has been observed in patients with neurodegeneration, and chemically sensitive individuals with asthma, migraine and MCS. In people with chemical sensitivity, these receptors are also sensitized, which is defined as a reduction in the threshold and an increase in the magnitude of a response to noxious stimulation. There is likely damage to the olfactory system in neurodegeneration and trigeminal nerve hypersensitivity in MCS, with different effects on olfactory processing. The associations of low vitamin D levels and protein kinase activity seen in neurodegeneration have not been studied in MCS. Table 2 presents a summary of neurodegeneration and MCS, comparing 16 distinctive genetic, pathophysiological and clinical features associated with air pollution exposures. There is significant overlap, suggesting potential comorbidity. Canadian Health Measures Survey data indicates an overlap between neurodegeneration and MCS (p < 0.05) that suggests comorbidity, but the extent of increased susceptibility to the other condition is not established. Nevertheless, the pathways to the development of these conditions likely involve TRPV1 and TRPA1 receptors, and so it is hypothesized that manifestation of neurodegeneration and/or MCS and possibly why there is divergence may be influenced by polymorphisms of these receptors, among other factors. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of guanidinoacetic acid (GAA) with different protein levels in feed on intestinal histomorphology, serum biochemistry, and meat quality of broiler chicken. GAA is the only direct precursor of creatine and is involved in the synthesis of bioenergy cellular. This research used 1.176 day-old chicks of the Lohmann Indian River strain that were reared for 35 days. The supplementation effect was investigated using six treatments, i.e., two levels of feed protein and three levels of GAA, with seven replications. Broiler chickens were fed with 23% and 21% crude protein during the pre-starter phase, 21% and 19% during the starter phase, and 19% and 17% during the finisher phase, with a GAA addition of 0 g/ton, 600 g/ton, and 1200 g/ton, respectively. The result showed GAA supplementation with different protein levels reduced triglyceride (P<0,05), cholesterol levels in serum (P<0,05), increased surface area of the microvilli (P<0,05), pH of breast meat (P<0,05), but did not affect the chemical quality of breast meat (P>0,05). In conclusion, GAA supplementation in different level protein diets increased the surface area of the microvilli, pH of breast meat, reduce serum cholesterol and triglycerides, without affecting the chemical quality of broiler meat. [ABSTRACT FROM AUTHOR]

Background: The shortage of primary care physicians in the United States is expected to grow to 17,800–48,000 physicians by 2034. Student Run Free Clinics are an increasingly popular component of medical schools and may provide an avenue for increasing medical student interest in primary care specialties. However, there is limited research on the impact of Student Run Free Clinics on medical student specialty choice. This investigation sought to determine whether volunteering with the Interprofessional Community Clinic (ICC), the Student Run Free Clinic associated with Chicago Medical School, was associated with an increased likelihood of matching into primary care specialties. Secondarily, the authors investigated associations between volunteering and matching into family practice. Finally, the authors explored associations between volunteering and the competitiveness of specialty choice. Methods: This retrospective review utilized data on medical school graduates from 2015 – 2021 including their matched specialties, the number of ICC shifts they volunteered for, and whether they held an ICC leadership position (executive officers). Primary care specialties were defined as internal medicine, family practice, pediatrics, or combined internal medicine/pediatrics. Residency fill rate was used as a proxy for competitiveness. Results: This analysis included 506 medical students (254 ICC volunteers and 252 non-volunteers). Among ICC volunteers, 47.2% matched into a primary care specialty compared to 36.5% of non-volunteers (RR 1.29, 95% CI 1.05–1.59). Each additional shift worked at the ICC was correlated with increased odds of matching into family practice by a factor of 1.042 (95% CI 1.005–1.079). Conclusions: Medical students who volunteered with the ICC were more likely to match into primary care residencies. Students who volunteered more frequently were more likely to match into family practice. Further investigation is warranted to determine whether these associations are causative and could thus be leveraged to encourage medical students to pursue primary care careers. [ABSTRACT FROM AUTHOR]

Background: Inhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foam macrophage formation. Results: The histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of total and foam macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages also significantly was increased. The gene and protein expression of a cholesterol transporter CD36, which is associated with lipid metabolism, was altered in the liver. The amount of selected cholesteryl esters (CE 16:0, CE 18:1, CE 20:4, CE 22:6) in liver tissue was decreased after subchronic PbO NP inhalation, while total and free cholesterol in liver tissue was slightly increased. Gene and protein expression of phospholipase PLCβ1 and receptor CD36 in human hepatocytes were affected also in in vitro experiments after acute PbO NP exposure. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in its interstitial tissues. Conclusion: Our study revealed the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and yet uncovered processes, which can contribute to steatosis in liver after metal nanoparticles exposure. [ABSTRACT FROM AUTHOR]

Background and Objectives: Student-directed activities such as family medicine interest groups (FMIG) and student-run free clinics (SRFC) have been examined to discover their impact on entry into family medicine and primary care. The objective of this review was to synthesize study results to better incorporate and optimize these activities to support family medicine and primary care choice.Methods: We conducted a comprehensive literature search using PubMed, Scopus, and CINAHL to identify all English-language research articles on FMIG and SRFC. We examined how participation relates to entry into family medicine and primary care specialties. Exclusion criteria were nonresearch articles, review articles, and research conducted outside the United States, Canada, Australia, and New Zealand. We used a 16-point quality rubric to evaluate 18 (11 FMIG, seven SRFC) articles that met our criteria.Results: Of the nine articles that examined whether FMIG participation impacted entry into family medicine, five papers noted a positive relationship, one paper noted unclear correlation, and three papers noted that FMIG did not impact entry into family medicine. Of the seven articles about SRFC, only one showed a positive relationship between SRFC activity and entry into primary care.Conclusions: Larger-scale and higher quality studies are necessary to determine the impact of FMIG and SRFC on entry into family medicine and primary care. However, available evidence supports that FMIG participation is positively associated with family medicine career choice. In contrast, SRFC participation is not clearly associated with primary care career choice. [ABSTRACT FROM AUTHOR]

Air pollution affects the majority of the world's population and has been linked to over 7 million premature deaths per year. Exposure to particulate matter (PM) contained within air pollution is associated with cardiovascular, respiratory, and neurological ill health. There is increasing evidence that exposure to air pollution in utero and in early childhood is associated with altered brain development. However, the underlying mechanisms for impaired brain development are not clear. While oxidative stress and neuroinflammation are documented consequences of PM exposure, cell-specific mechanisms that may be triggered in response to air pollution exposure are less well defined. Here, we assess the effect of urban PM exposure on two different cell types, microglial-like BV2 cells and neural stem/precursor-like C17.2 cells. We found that, contrary to expectations, immature C17.2 cells were more resistant to PM-mediated oxidative stress and cell death than BV2 cells. PM exposure resulted in decreased mitochondrial health and increased mitochondrial ROS in BV2 cells which could be prevented by MitoTEMPO antioxidant treatment. Our data suggest that not only is mitochondrial dysfunction a key trigger in PM-mediated cytotoxicity but that such deleterious effects may also depend on cell type and maturity. [ABSTRACT FROM AUTHOR]

The increasing amount of particulate matter (PM) in the ambient air is a pressing public health issue globally. Epidemiological studies involving data from millions of patients or volunteers have associated PM with increased risk of dementia and Alzheimer's disease in the elderly and cognitive dysfunction and neurodegenerative pathology across all age groups, suggesting that PM may be a risk factor for neurodegenerative diseases. Neurodegenerative diseases affect an increasing population in this aging society, putting a heavy burden on economics and family. Therefore, understanding the mechanism by which PM contributes to neurodegeneration is essential to develop effective interventions. Evidence in human and animal studies suggested that PM induced neurodenegerative-like pathology including neurotoxicity, neuroinflammation, oxidative stress, and damage in blood–brain barrier and neurovascular units, which may contribute to the increased risk of neurodegeneration. Interestingly, antagonizing oxidative stress alleviated the neurotoxicity of PM, which may underlie the essential role of oxidative stress in PM's potential effect in neurodegeneration. This review summarized up-to-date epidemiological and experimental studies on the pathogenic role of PM in neurodegenerative diseases and discussed the possible underlying mechanisms. [ABSTRACT FROM AUTHOR]

The use of low-NOx compressed natural gas (CNG) medium-duty vehicles (MDVs) and heavy-duty vehicles (HDVs) has the potential to significantly reduce NOx emissions and yield improvements in regional air quality. However, the extent of air quality improvement depends on many factors including future levels of vehicle deployment, the evolution of emissions from other sources, and meteorology. An analysis of the impacts requires modeling the atmosphere to account for both primary and secondary air pollutants, and the use of health impact assessment tools to map air quality changes into quantifiable metrics of human health. Here, we quantify and compare the air quality and health impacts associated with the deployment of low-NOx CNG engines to power future MDV and HDV fleets in California relative to both a business-as-usual and a more advanced fleet composition. The results project that reductions in summer ground-level ozone could reach 13 ppb when compared to a baseline fleet of diesel and gasoline HDV and MDV and could reach 6 ppb when compared to a cleaner fleet that includes some zero-emission vehicles and fuels. Similarly, for all CNG cases considered reductions in PM2.5 are predicted to range from 1.2 ug/m3 to 2.7 ug/m3 for a summer episode and from 3.1 ug/m3 to approximately 7.8 ug/m3 for a winter episode. These improvements yield short-term health benefits equivalent to $47 to $56 million in summer and $38 to $43 million in winter during episodes conducive to poor air quality. Additionally, the use of zero emission vehicle options such as battery electric and hydrogen fuel cell trucks could achieve approximately 25% to 31% higher benefits for an equivalent fleet penetration level due to the additional emission reductions achieved. Implications: The paper provides a quantitative estimate of the air quality and human health benefits that can be achieved through the use of novel compressed natural gas engines (i.e., low-NOx CNG) in medium- and heavy-duty vehicles and provide a comparison with zero emission vehicles. Thus, our findings will provide support for policy development seeking to transform the trucking sector to meet clean air and climate goals given the current struggle policymakers have with selecting between alternative truck technologies due to variance in factors like cost and technical maturity. [ABSTRACT FROM AUTHOR]

Objectives: The Coronavirus disease 2019 (COVID-19) pandemic disrupted medical student education, particularly in New York City (NYC). We aimed to assess the impact of the COVID-19 pandemic on medical students' residency choices. Methods: The authors conducted a cross-sectional survey of medical students in all years of study at four NYC medical schools (Columbia, Cornell, NYU, and SUNY Downstate). The survey was fielded from 19 Aug 2020 to 21 Sep 2020. Survey questions included items assessing COVID-19 impact on residency choices, personal impact of COVID-19, residency/specialty choices, and factors influencing these choices. Results: A total of 2310 students received the survey, with 547 (23.7%) providing partial responses and 212 (9.2%) providing valid responses for our primary analysis. 59.0% of participants thought that COVID-19 influenced their choice of residency/specialty, with 0.9% saying the influence was to a great extent, 22.2% to some extent, and 35.8% very little. On multivariable analysis, factors that were independently associated with COVID-19 impacting residency choice included low debt ($1 to $99,999: adjOR 2.23, 95%CI 1.02–5.03) compared with no debt and Other race/ethnicity (adjOR 0.26, 95%CI 0.10–0.63) compared with White race/ethnicity. On secondary analysis of all participants answering survey items for logistic regression regardless of survey completion, direct personal impact of COVID-19 was significantly associated with COVID-19 impacting specialty choice (adjOR 1.90, 95%CI 1.04–3.52). Moreover, 24 students (11.6%) reported a change in their top residency choice from before to during/after COVID-19, citing concerns about frontline work, work-life balance, and risk of harm. Conclusions: Our study found that 3 in 5 (59.0%) participants felt that COVID-19 impacted their residency choice, with 11.6% of respondents explicitly changing their top specialty choice. Investigating the impact of the pandemic on medical student residency considerations is crucial to understand how medical career outlooks may change in the future. [ABSTRACT FROM AUTHOR]

Air pollution (AP) triggers neuroinflammation and lipoperoxidation involved in physiopathology of several neurodegenerative diseases. Our study aims to investigate the effect of chronic exposure to ambient AP in oxidative stress (OS) parameters and number of neurons and microglial cells of the cortex and striatum. Seventy-two male Wistar rats were distributed in four groups of exposure: control group (FA), exposed throughout life to filtered air; group PA-FA, pre-natal exposed to polluted air until weaning and then to filtered air; group FA-PA, pre-natal exposed to filtered air until weaning and then to polluted air; and group PA, exposed throughout life to polluted air. After 150 days of exposure, the rats were euthanized for biochemical and histological determinations. The malondialdehyde concentration in the cortex and striatum was significantly higher in the PA group. The activity of superoxide dismutase was significantly decreased in the cortex of all groups exposed to AP while activity of catalase was not modified in the cortex or striatum. The total glutathione concentration was lower in the cortex and higher in the striatum of the FA-PA group. The number of neurons or microglia in the striatum did not differ between FA and PA. On the other hand, neurons and microglia cell numbers were significantly higher in the cortex of the FA-PA group. Our findings suggest that the striatum and cortex have dissimilar thresholds to react to AP exposure and different adaptable responses to chronically AP-induced OS. At least for the cortex, changing to a non-polluted ambient early in life was able to avoid and/or reverse the OS, although some alterations in enzymatic antioxidant system may be permanent. As a result, it is important to clarify the effects of AP in the cortical organization and function because of limited capacity of brain tissue to deal with threatening environments. [ABSTRACT FROM AUTHOR]

The World Health Organisation recently listed air pollution as the most significant threat to human health. Air pollution comprises particulate matter (PM), metals, black carbon and gases such as ozone (O3), nitrogen dioxide (NO2) and carbon monoxide (CO). In addition to respiratory and cardiovascular disease, PM exposure is linked with increased risk of neurodegeneration as well as neurodevelopmental impairments. Critically, studies suggest that PM crosses the placenta, making direct in utero exposure a reality. Rodent models reveal that neuroinflammation, neurotransmitter imbalance and oxidative stress are triggered following gestational/early life exposure to PM, and may be exacerbated by concomitant mitochondrial dysfunction. Gestational PM exposure (potentiated by mitochondrial impairment in the metabolically active neonatal brain) not only impacts neurodevelopment but may sensitise the brain to subsequent cognitive impairment. Having reviewed this field, we conclude that strategies are urgently required to reduce exposure to PM during this sensitive developmental period. [ABSTRACT FROM AUTHOR]

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD. [ABSTRACT FROM AUTHOR]

Purpose: As the need for effective physician leaders caring for underserved populations grows, it is important to initiate interventions for medical professionals early in their education. Board experience on a student-run free clinic serving vulnerable populations within the community has the potential to educate medical students in a hands-on environment. This paper aims to determine if serving as a leader of a student-run free clinic impacts leadership skills and future leadership goals of medical students. Design/methodology/approach: Medical students leading a student-run free clinic completed an anonymous electronic survey to determine how this experience affected their teamwork skills, interprofessional leadership skills and future leadership career goals. The survey consisted of 12 items to which students responded with how closely they agreed via a five-point Likert scale with 1 = strongly disagree and 5 = strongly agree. Descriptive statistics are reported. Findings: From the 46 students (42.2% response rate) responding to the survey, 95.45% had a previous leadership experience and 89.2% expressed previous interest in a leadership position. Students scored on average 4.36 (out of 5) for improvement in teamwork skills, 4.34 (out of 5) for improvement in interprofessional skills and 3.88 (out of 5) for impact on future leadership career goals. Originality/value: This study suggests that service on a student-run free clinic improves teamwork and interprofessional leadership skills as well as future leadership plans of medical students in an underserved vulnerable population environment. Other institutions could use student-run free clinics for early development of effective leaders in medical health care for the vulnerable population. [ABSTRACT FROM AUTHOR]

A growing number of studies have shown that air fine particulate matter (PM2.5) pollution is closely associated with neuroinflammation in humans. Militarine, a glucosyloxybenzyl 2-isobutylmalate compound isolated from Bletilla striata, has been found to exert significant neuroprotective effects. However, the anti-inflammatory, antioxidant and antiapoptotic effects of militarine on PM2.5-stimulated BV-2 microglial cells have not been reported. This study aimed to investigate the protective effects of militarine against PM2.5-induced cytotoxicity and its mechanism in BV-2 microglial cells. Our results revealed that pretreatment with 0.31–1.25 μg/mL militarine reversed the morphological changes caused by PM2.5 and decreased proinflammatory cytokine generation and gene expression in PM2.5-treated BV-2 cells. In particular, tumor necrosis factor-α and interleukin-6 expression was inhibited in a dose-dependent manner. Notably, militarine markedly inhibited the upregulation of Toll-like receptor 4, Toll-like receptor 2, and cyclo-oxygenase-2 expression at both the mRNA and protein levels and reduced NF-κB pathway-associated protein expression. Immunofluorescence analysis showed that militarine suppressed NF‐κB activity through inhibiting p65 nuclear translocation. Our data suggested that militarine alleviated neuroinflammation in BV-2 microglial cells, possibly by inhibiting the expression of neuroinflammatory cytokines through the TLR/NF-κB signaling pathway. Additionally, militarine significantly reduced PM2.5-mediated reactive oxygen species (ROS) generation and cell apoptosis and restored the mitochondrial membrane potential (MMP; ΔΨm). Collectively, these findings demonstrate that militarine played a protective role against PM2.5‐induced damage in BV-2 cells by exerting anti-inflammatory, antioxidant, and antiapoptotic effects. [ABSTRACT FROM AUTHOR]

Many reports have shown a strong association between exposure to neurotoxic air pollutants like heavy metal and particulate matter (PM) as an active participant and neurological disorders. While the effects of these toxic pollutants on cardiopulmonary morbidity have principally been studied, growing evidence has shown that exposure to polluted air is associated with memory impairment, communication deficits, and anxiety/depression among all ages. So, these toxic pollutants in the environment increase the risk of neurodegenerative disease, ischemia, and autism spectrum disorders (ASD). The precise mechanisms in which air pollutants lead to communicative inability, social inability, and declined cognition have remained unknown. Various animal model studies show that amyloid precursor protein (APP), processing, oxidant/antioxidant balance, and inflammation pathways change following the exposure to constituents of polluted air. In the present review study, we collect the probable molecular mechanisms of deleterious CNS effects in response to various air pollutants. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that particulate matter 2.5 (PM2.5) exposure stimulates systemic inflammation and activates the hypothalamus–pituitary–adrenal (HPA) axis, both of which are associated with stroke incidence and mortality. However, whether filtered air (FA) intervention modulates inflammation and HPA axis activation is still largely unknown. For FA group and PM2.5 group, adult Sprague-Dawley male and female rats were exposed to FA or PM2.5 for 6 months, respectively. For PM2.5 + 15 days FA group, the rats were achieved by receiving 15 days FA after PM2.5 exposure for 6 months. The immune cells and inflammatory biomarker levels in the blood and brain were analyzed by flow cytometry, ELISA, and qRT-PCR. To assess HPA axis activation, the levels of hormones in the blood were also analyzed by ELISA. FA intervention increased the percentage of CD4 T cells and T cells in the blood, which had decreased after PM2.5 exposure in both male and female rats. The ELISA and qRT-PCR results showed that FA intervention significantly reduced the levels of inflammatory biomarkers in the peripheral blood, and alleviated neuroinflammation in the cortex, hippocampus, and striatum. In addition, FA intervention also inhibited the inflammation in the hypothalamus and pituitary and adrenal glands, and decreased the levels of HPA axis hormones. Our results indicate that FA intervention exerts a protective effect on the brain by decreasing inflammation and HPA axis activation after PM2.5 exposure in both male and female rats. [ABSTRACT FROM AUTHOR]

Objective: The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Materials and Methods: Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI. Results and Discussion: Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal. Conclusions: Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use. [ABSTRACT FROM AUTHOR]

Attractive due to an alleged high biocompatibility, silica nanoparticles have been widely used in the field of nanomedicine; however, their proven capacity to induce the synthesis and release of pro-inflammatory cytokines in several cellular models has raised concern about their safety. Glutamate, the main excitatory amino acid transmitter triggers a wide variety of signal transduction cascades that regulate protein synthesis at transcriptional and translational levels. A stimulus-dependent dynamic change in the protein repertoire in neurons and glia cells is the molecular framework of higher brain functions. Within the cerebellum, Bergmann glia cells are the most abundant non-neuronal cells and span the entire molecular layer of the cerebellar cortex, wrapping the synapses in this structure. Taking into consideration the functional role of Bergmann glia in terms of the recycling of glutamate, lactate supply to neurons, and prevention of neurotoxic insults, we decided to investigate the possibility that silica nanoparticles affect Bergmann glia and by these means alter the major excitatory neurotransmitter system in the brain. To this end, we exposed cultured chick cerebellar Bergmann glia cells to silica nanoparticles and measured [35S]-methionine incorporation into newly synthesized polypeptides. Our results demonstrate that exposure of the cultured cells to silica nanoparticles exerts a time- and dose-dependent modulation of protein synthesis. Furthermore, altered patterns of eukaryotic initiation factor 2 alpha and eukaryotic elongation factor 2 phosphorylation were present upon nanoparticle exposure. These results demonstrate that glia cells respond to the presence of this nanomaterial modifying their proteome, presumably in an effort to overcome any plausible neurotoxic effect. [ABSTRACT FROM AUTHOR]

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains. [ABSTRACT FROM AUTHOR]

Background: The choice of medical specialty is related to multiple factors, students' values, and specialty perceptions. Research in this area is needed in low- and middle-income countries, where the alignment of specialty training with national healthcare needs has a complex local interdependency. The study aimed to identify factors that influence specialty choice among medical students. Methods: Senior students at the National Autonomous University of Mexico (UNAM) Faculty of Medicine answered a questionnaire covering demographics, personal experiences, vocational features, and other factors related to specialty choice. Chi-square tests and factor analyses were performed. Results: The questionnaire was applied to 714 fifth-year students, and 697 provided complete responses (response rate 81%). The instrument Cronbach's alpha was 0.8. The mean age was 24 ± 1 years; 65% were women. Eighty percent of the students wanted to specialize, and 60% had participated in congresses related to the specialty of interest. Only 5% wanted to remain as general practitioners. The majority (80%) wanted to enter a core specialty: internal medicine (29%), general surgery (24%), pediatrics (11%), gynecology and obstetrics (11%) and family medicine (4%). The relevant variables for specialty choice were grouped in three dimensions: personal values that develop and change during undergraduate training, career needs to be satisfied, and perception of specialty characteristics. Conclusions: Specialty choice of medical students in a middle-income country public university is influenced by the undergraduate experience, the desire to study a subspecialty and other factors (including having skills related to the specialty and type of patients). [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) released by the burning of domestic solid fuels is an important air pollutant in the rural indoor environment in China. Here, personal exposure to PM2.5-induced oxidative damage resulting from household solid fuel combustion was examined in winter in rural areas of Guanzhong Basin, northwestern China. The volume-based average exogenous reactive oxygen species (exo-ROS) activities were 1943.7 ± 3668.0 and 1628.5 ± 2618.7 μM H2O2/min/m3 for 50 and 100 μL of PM2.5 extracts, respectively. While the different patterns were found for endogenous reactive oxygen species (endo-ROS), 465.8 ± 2427.4 and 1740.4 ± 2643.2 μM H2O2/min/m3 for 4 h exposed to 50 and 100 μL of PM2.5 extract. When the exposure time was extended to 24 h, endo-ROS activities were 3789.5 ± 4582.0 and 3534.8 ± 4595.6 μM H2O2/min/m3 for 50 and 100 μL of PM2.5 extracts, respectively. Among four common dwelling heating ways used in northwestern China, the highest ROS activity (160.4 μM H2O2/min/m3 for 4-h endo-ROS at 50 μL of PM2.5 extracts) was found for households using indoor coal chunks stove. The ROS activity in households using electric power heating was 2.9–15.9-fold lower than that in households using indoor coal chunks stove; thus, electric power heating was found to be the cleanest method for rural household heating. PM2.5-bound K+, organic carbon 1 (OC1), elemental carbon 1 (EC1), several polycyclic aromatic hydrocarbons (PAHs), and two hopanes species were observed to be significantly correlated with exo-ROS and 4-h endo-ROS, indicating that these chemical compounds and the sources in PM2.5 exposure samples may induce more ROS and affect human health strongly. The results indicate that heating methods used in rural households in winter can greatly impact the health of residents living in rural areas of northwestern China through personal exposure PM2.5-induced oxidative damage. [ABSTRACT FROM AUTHOR]

Objectives: Rodents used in scientific research are typically housed in cages containing natural bedding materials. Despite extensive evidence of biological harm from inhaled particulate matter (PM), relatively little work has been performed to measure bedding-generated PM exposure in caged animals used in basic science research. Our objectives were to determine whether bedding-generated PM was present in significant concentrations in rodent cages and to identify the main factors affecting the accumulation and attenuation of bedding-generated PM inside cages. Materials and Methods: We measured PM2.5 concentrations in cages containing common bedding materials (pine, aspen, paper, and corncob) with filter top isolator absent or present on the cages. PM2.5 concentrations were monitored with rats inside cages as well as during artificial manipulation of the bedding (designed to simulate rodent activity). Results and Discussion: Upon rodent digging or mechanical/manual stirring, all four bedding materials produced significant increases in PM2.5 concentrations (as much as 100–200 µg/m3 PM2.5, 50- to 100-fold higher than during periods of no rodent activity), and concentrations in cages fitted with filter tops were an order of magnitude higher than in cages without filter tops. Elevated concentrations were sustained for longer durations in cages with filter tops (5–10 minutes) compared to cages with only bar lids (0–2 minutes). Conclusions: These results indicate that standard laboratory housing conditions can expose rodents to substantial levels of PM2.5. Bedding-generated PM has potential implications as an environmental agent in rodent studies. [ABSTRACT FROM AUTHOR]

1. The present experiment was designed to examine arginine (Arg)-sparing effects of guanidinoacetic acid (GAA) on production performance, intestinal morphology and certain blood parameters in broiler chickens. 2. A total of 300 male broiler chicks (Ross 308) were randomly allotted to 5 dietary treatments in a completely randomised design during 1-15 and 15-35 d rearing periods. Experimental treatments consisted of a basal diet with a reduction in Arg content (CON−; starter: 12.1 g/kg and grower: 11.3 g/kg Arg), a CON− diet supplemented with synthetic Arg equal to the required Arg level (CON+; starter: 13.80 g/kg; grower: 12.37 g/kg) and CON− diet supplemented with three levels of GAA (GAA0.6; GAA1.2; and GAA1.8; g/kg). 3. Supplemental GAA at 0.6 and 1.2 g/kg reduced the adverse effects of the CON− diet on weight gain and feed conversion ratio in the starter period, equal to the effect of CON+ diet. During the entire rearing period, such an effect was only seen for broilers fed CON− diet supplemented with 1.2 and 1.8 g/kg GAA (P < 0.05). Proportional weights of liver and abdominal fat were decreased in birds fed diets containing supplemental Arg and 1.8 g/kg GAA compared to the CON− broilers (P < 0.05). Jejunal villus height and villus height to crypt depth ratio were increased in broilers receiving the CON− diet (P < 0.05). Serum concentration of nitric oxide increased when the CON− diet was supplemented with either Arg or 1.8 g/kg GAA (P < 0.05). 4. Dietary inclusion of GAA had an Arg-sparing effect, whereby 1.2 and 1.8 g/kg of supplemental GAA resulted in greater growth performance during the starter and entire rearing periods, respectively. Supplementation with 1.8 g/kg GAA had significant effects on some carcass and physiological parameters. [ABSTRACT FROM AUTHOR]

It was reported that in vitro short-term exposure to PM2.5 caused different lung diseases through inflammatory response, immune toxicity, oxidative stress, and genetic mutations. However, the complex molecular biological mechanism for its toxicity had not been fully elucidated. Therefore, the present study investigated the cytotoxicity, oxidative damage, mitochondria damage, apoptosis, and cell cycle arrest of NX and QH PM2.5 in A549 cells. Further, cell cycle arrest-related gene levels in PM2.5-induced A549 cells were also detected. Our results suggested that PM2.5 reduced the cell viability in A549 cells. Simultaneously, excessive ROS decreased MMP levels and damaged mitochondrial membrane integrity and induced mitochondrial oxidative damage through the oxygen-dependent killer route, resulting in mitochondrial damage and cell apoptosis. Besides, the results also showed that PM2.5 induced A549 cell cycle alteration in G2/M phase after co-culture for 24 h. G2/M phase arrest was induced by upregulation of p53 and p21 and downregulation of CDK1 mRNA expression. In addition, lncRNA Sox2ot might play an important role as the specific oncogenes and it participated in G2/M phase arrest by regulating the expression of EZH2. [ABSTRACT FROM AUTHOR]

While the impact of emissions from combustion of fossil fuel on human health has been extensively studied, current knowledge of exhaust exposure from combustion of biofuels provides limited and inconsistent information about its neurotoxicity. The objective of the present work was to compare the gene expression patterns in rat frontal cortex and hippocampus after exposure to diesel exhaust emissions (DEE) from combustion of two 1st generation fuels, 7% fatty acid methyl esters (FAME) (B7) and 20% FAME (B20), and a 2nd generation 20% FAME/hydrotreated vegetable oil (SHB20: synthetic hydrocarbon biofuel), with and without diesel particulate filter (DPF). The Fisher 344 rats (n = 7/treatment) were exposed to DEE for 7 days (6h/day), and for 28 days (6h/day, 5 days/week) in whole body exposure chambers. The controls were breathing room air. Brain histological examinations did not reveal any adverse exposure-related effects of DEE in frontal cortex or in hippocampus. Gene expression analysis showed that several genes associated with antioxidant defenses and inflammation were statistically differently expressed in DEE exposed animals versus control. In addition, the gene expression changes between the exposure groups were compared, where the observed rank order in frontal cortex was B7 > B20 > SHB20 after 7 days of exposure, and SHB20 > B7 = B20 after 28 days of exposure. In the hippocampus, the rank order was B7 > SHB20 > B20. Effect of DPF treatment was observed for Tnf only. Overall, moderate increases in bio-components in diesel blends do not appear to result in dramatic alterations in gene expression or adverse histopathological effects. [ABSTRACT FROM AUTHOR]

The World Health Organization lists air pollution as one of the top five risks for developing chronic non-communicable disease, joining tobacco use, harmful use of alcohol, unhealthy diets and physical inactivity. This review focuses on how host defense mechanisms against adverse airborne exposures relate to the probable interacting and overlapping pathophysiological features of neurodegeneration and multiple chemical sensitivity. Significant long-term airborne exposures can contribute to oxidative stress, systemic inflammation, transient receptor subfamily vanilloid 1 (TRPV1) and subfamily ankyrin 1 (TRPA1) upregulation and sensitization, with impacts on olfactory and trigeminal nerve function, and eventual loss of brain mass. The potential for neurologic dysfunction, including decreased cognition, chronic pain and central sensitization related to airborne contaminants, can be magnified by genetic polymorphisms that result in less effective detoxification. Onset of neurodegenerative disorders is subtle, with early loss of brain mass and loss of sense of smell. Onset of MCS may be gradual following long-term low dose airborne exposures, or acute following a recognizable exposure. Upregulation of chemosensitive TRPV1 and TRPA1 polymodal receptors has been observed in patients with neurodegeneration, and chemically sensitive individuals with asthma, migraine and MCS. In people with chemical sensitivity, these receptors are also sensitized, which is defined as a reduction in the threshold and an increase in the magnitude of a response to noxious stimulation. There is likely damage to the olfactory system in neurodegeneration and trigeminal nerve hypersensitivity in MCS, with different effects on olfactory processing. The associations of low vitamin D levels and protein kinase activity seen in neurodegeneration have not been studied in MCS. Table 2 presents a summary of neurodegeneration and MCS, comparing 16 distinctive genetic, pathophysiological and clinical features associated with air pollution exposures. There is significant overlap, suggesting potential comorbidity. Canadian Health Measures Survey data indicates an overlap between neurodegeneration and MCS (p < 0.05) that suggests comorbidity, but the extent of increased susceptibility to the other condition is not established. Nevertheless, the pathways to the development of these conditions likely involve TRPV1 and TRPA1 receptors, and so it is hypothesized that manifestation of neurodegeneration and/or MCS and possibly why there is divergence may be influenced by polymorphisms of these receptors, among other factors., (© 2021 John Molot et al., published by De Gruyter, Berlin/Boston.)

Background: Air pollution is a recognized aggravating factor for pulmonary diseases and has notably deleterious effects on asthma, bronchitis and pneumonia. Recent studies suggest that air pollution may also cause adverse effects in the gastrointestinal tract. Accumulating experimental evidence shows that immune responses in the pulmonary and intestinal mucosae are closely interrelated, and that gut-lung crosstalk controls pathophysiological processes such as responses to cigarette smoke and influenza virus infection. Our first aim was to collect urban coarse particulate matter (PM) and to characterize them for elemental content, gastric bioaccessibility, and oxidative potential; our second aim was to determine the short-term effects of urban coarse PM inhalation on pulmonary and colonic mucosae in mice, and to test the hypothesis that the well-known antioxidant N-acetyl-L-cysteine (NAC) reverses the effects of PM inhalation. Results: The collected PM had classical features of urban particles and possessed oxidative potential partly attributable to their metal fraction. Bioaccessibility study confirmed the high solubility of some metals at the gastric level. Male mice were exposed to urban coarse PM in a ventilated inhalation chamber for 15 days at a concentration relevant to episodic elevation peak of air pollution. Coarse PM inhalation induced systemic oxidative stress, recruited immune cells to the lung, and increased cytokine levels in the lung and colon. Concomitant oral administration of NAC reversed all the observed effects relative to the inhalation of coarse PM. Conclusions: Coarse PM-induced low-grade inflammation in the lung and colon is mediated by oxidative stress and deserves more investigation as potentiating factor for inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer's Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0.95 mg/m3, 6 h/day, 5 days/week) or clean air (controls) behaviour tests were performed and amyloid-β (Aβ) plaque formation, pulmonary histopathology and systemic inflammation were evaluated. Results: In a string suspension task, assessing for grip strength and motor coordination, 13 weeks exposed 5XFAD mice performed significantly less than the 5XFAD controls. Spatial working memory deficits, assessed by Y-maze and X-maze tasks, were not observed in association with the DEE exposures. Brains of the 3 weeks DEE-exposed 5XFAD mice showed significantly higher cortical Aβ plaque load and higher whole brain homogenate Aβ42 levels than the clean air-exposed 5XFAD littermate controls. After the 13 weeks exposures, with increasing age and progression of the AD-phenotype of the 5XFAD mice, DEE-related differences in amyloid pathology were no longer present. Immunohistochemical evaluation of lungs of the mice revealed no obvious genetic background-related differences in tissue structure, and the DEE exposure did not cause histopathological changes in the mice of both backgrounds. Luminex analysis of plasma cytokines demonstrated absence of sustained systemic inflammation upon DEE exposure. Conclusions: Inhalation exposure to DEE causes accelerated plaque formation and motor function impairment in 5XFAD transgenic mice. Our study provides further support that the brain is a relevant target for the effects of inhaled DEE and suggests that long-term exposure to this ubiquitous air pollution mixture may promote the development of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders. In this article, we first briefly summarize the pathophysiological role of TLRs in the inflammatory diseases. We then focus on reviewing the current knowledge in both preclinical and clinical studies of various TLR antagonists/inhibitors for the prevention and treatment of inflammatory diseases. These compounds range from conventional small molecules to therapeutic biologics and nanodevices. In particular, nanodevices are emerging as a new class of potent TLR inhibitors for their unique properties in desired bio-distribution, sustained circulation, and preferred pharmacodynamic and pharmacokinetic profiles. More interestingly, the inhibitory activity of these nanodevices can be regulated through precise nano-functionalization, making them the next generation therapeutics or "nano-drugs." Although, significant efforts have been made in developing different kinds of new TLR inhibitors/antagonists, only limited numbers of them have undergone clinical trials, and none have been approved for clinical uses to date. Nevertheless, these findings and continuous studies of TLR inhibition highlight the pharmacological regulation of TLR signaling, especially on multiple TLR pathways, as future promising therapeutic strategy for various inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). [ABSTRACT FROM AUTHOR]

Particulate matter (PM) combined with meteorological factors cause the haze, which brings inconvenience to people's daily life and deeply endanger people's health. Accumulating literature, to date, reported that PM are closely related to cardiopulmonary disease. Outpatient visits and admissions as a result of asthma and heart attacks gradually increase with an elevated concentration of PM. Owing to its special physicochemical property, the brain could be a potential target beyond the cardiopulmonary system. Possible routes of PM to the brain via a direct route or stimulation of pro-inflammatory cytokines have been reported in several documents concerning toxicity of engineered nanoparticles in rodents. Recent studies have demonstrated that PM have implications in oxidative stress, inflammation, dysfunction of cellular organelles, as well as the disturbance of protein homeostasis, promoting neuron loss and exaggerating the burden of central nervous system (CNS). Moreover, the smallest particles (nano-sized particles), which were involved in inflammation, reactive oxygen species (ROS), microglial activation and neuron loss, may accelerate the process of the neurodevelopmental disorder and neurodegenerative disease. Potential or other undiscovered mechanisms are not mutually exclusive but complementary aspects of each other. Epidemiology studies have shown that exposure to PM could bring about neurotoxicity and play a significant role in the etiology of CNS disease, which has been gradually corroborated by in vivo and in vitro studies. This review highlights research advances on the health effects of PM with an emphasis on neurotoxicity. With the hope of enhancing awareness in the public and calling for prevention and protective measures, it is a critical topic that requires proceeding exploration. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ambient particulate matter (PM), a component of air pollution, exacerbates airway inflammation and hyperreactivity in asthmatic patients. Studies showed that PM possesses adjuvant-like properties that enhance the allergic inflammatory response; however, the mechanism (or mechanisms) by which PM enhances the allergic response remains to be determined. The aim of this study was to assess how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway immune response in BALB/cmice undergoing sensitization and challenge with ovalbumin (OVA). Eight-week-old BALB/cmale mice were sensitized/challenged with phosphate-buffered saline (PBS/PBS;n= 6), PM/PBS (n= 6), OVA/OVA (n= 6), or OVA + PM/OVA (n= 6). Lung tissue, bronchoalveolar lavage fluid (BALF), and plasma were analyzed for cellular inflammation, cytokines, immunoglobulin E, and heme oxygenase-1 (HO-1) expression. Mice in the OVA + PM/OVA group displayed significantly increased airway inflammation compared to OVA/OVA animals. Total cells, macrophages, and eosinophils recovered in BALF were significantly elevated in the OVA + PM/OVA compared to OVA/OVA group. Histopathological grading indicated that OVA + PM/OVA treatment induced significant inflammation compared to OVA/OVA. Both immunoglobulin (Ig) E and tumor necrosis factor (TNF) α levels were significantly increased in OVA/OVA and OVA + PM /OVA groups compared to PBS/PBS control. The number of HO-1 positive alveolar macrophages was significantly elevated in lungs of mice treated with OVA + PM /OVA compared to OVA/OVA. Our findings suggest that fine PM enhances allergic inflammatory response in pulmonary tissue through mechanisms involving increased oxidative stress. [ABSTRACT FROM AUTHOR]

A growing number of studies have shown that air fine particulate matter (PM 2.5 ) pollution is closely associated with neuroinflammation in humans. Militarine, a glucosyloxybenzyl 2-isobutylmalate compound isolated from Bletilla striata, has been found to exert significant neuroprotective effects. However, the anti-inflammatory, antioxidant and antiapoptotic effects of militarine on PM 2.5 -stimulated BV-2 microglial cells have not been reported. This study aimed to investigate the protective effects of militarine against PM 2.5 -induced cytotoxicity and its mechanism in BV-2 microglial cells. Our results revealed that pretreatment with 0.31-1.25 μg/mL militarine reversed the morphological changes caused by PM 2.5 and decreased proinflammatory cytokine generation and gene expression in PM 2.5 -treated BV-2 cells. In particular, tumor necrosis factor-α and interleukin-6 expression was inhibited in a dose-dependent manner. Notably, militarine markedly inhibited the upregulation of Toll-like receptor 4, Toll-like receptor 2, and cyclo-oxygenase-2 expression at both the mRNA and protein levels and reduced NF-κB pathway-associated protein expression. Immunofluorescence analysis showed that militarine suppressed NF-κB activity through inhibiting p65 nuclear translocation. Our data suggested that militarine alleviated neuroinflammation in BV-2 microglial cells, possibly by inhibiting the expression of neuroinflammatory cytokines through the TLR/NF-κB signaling pathway. Additionally, militarine significantly reduced PM 2.5 -mediated reactive oxygen species (ROS) generation and cell apoptosis and restored the mitochondrial membrane potential (MMP; ΔΨm). Collectively, these findings demonstrate that militarine played a protective role against PM 2.5 -induced damage in BV-2 cells by exerting anti-inflammatory, antioxidant, and antiapoptotic effects.

BACKGROUND: Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (OBJECTIVE: We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 μm in diameter (PM10) and < 2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk. METHODS: Our nested case--control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders. RESULTS: We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORq5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations. CONCLUSIONS: Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. CITATION: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759-1765; http://dx.doi.org/10.1289/EHP135 [ABSTRACT FROM AUTHOR]

BACKGROUND: Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. OBJECTIVES: To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. METHODS: We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. RESULTS: We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. CONCLUSIONS: Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution--related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. CITATION: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683-1693; http://dx.doi.org/10.1289/EHP136 [ABSTRACT FROM AUTHOR]

Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V2O3, V2O4, and V2O5, which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO4(+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V2O5was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO4was more toxic than the V2O5particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia, used to prevent disease recurrence in the brain, is essential for survival. Systemic and intrathecal methotrexate, commonly used for CNS-directed treatment, have been associated with cognitive problems during and after treatment. The cortex, hippocampus, and caudate putamen, important brain regions for learning and memory, may be involved in methotrexate-induced brain injury. Objectives of this study were to (1) quantify neuronal degeneration in selected regions of the cortex, hippocampus, and caudate putamen and (2) measure changes in the expression of genes with known roles in oxidant defense, apoptosis/inflammation, and protection from injury. Male Sprague Dawley rats were administered 2 or 4 mg/kg of methotrexate diluted in artificial cerebrospinal fluid (aCSF) or aCSF only into the left cerebral lateral ventricle. Gene expression changes were measured using customized reverse transcription (RT)2 polymerase chain reaction arrays. The greatest percentage of degenerating neurons in methotrexate-treated animals was in the medial region of the cortex; percentage of degenerating neurons in the dentate gyrus and cornu ammonis 3 regions of the hippocampus was also greater in rats treated with methotrexate compared to perfusion and vehicle controls. There was a greater percentage of degenerating neurons in the inferior cortex of control versus methotrexate-treated animals. Eight genes involved in protection from injury, oxidant defense, and apoptosis/inflammation were significantly downregulated in different brain regions of methotrexate-treated rats. To our knowledge, this is the first study to investigate methotrexate-induced injury in selected brain regions and gene expression changes using a rat model of intraventricular drug administration. [ABSTRACT FROM AUTHOR]