We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in alreadysensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVAsensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects. allergic inflammation; oxidative stress; distal lung AMBIENT PARTICULATE MATTER (PM) exposure is a contributing factor to increased respiratory morbidity and mortality in an urban environment (37,48,51). Epidemiological studies have demonstrated that increased asthma prevalence, including the number of patients diagnosed with the disease as well as asthma-related hospital visits, is closely associated with PM levels in the ambient air, the regional motor vehicle traffic density, and residential proximity to freeways (21,47,52,53). Several mechanisms have been proposed to explain PM effects in asthma (44). While acute asthma flares in response to vehicle emission may be caused by an exacerbation of existing airway inflammation or airway hyperreactivity, the possibility also needs to be entertained that the increase in allergic inflammation could originate at the level of boosting of the secondary immune response to common environmental allergens in already-sensitized people (11-13, 30, 45). This would be a logical extension of the idea that ambient PM or diesel exhaust particle (DEP) exposure acts as an adjuvant that can lead to a de novo priming of the immune response to common environmental or experimental allergen (11-13, 30, 36, 45). We have recently confirmed that intranasal instillation of ambient ultrafine particles (UFP) derived from vehicular emissions close to a major Los Angeles freeway is capable of generating a new immune response to ovalbumin (OVA) in Balb/c mi...

To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 µg/m3), fine (178 µg/m3) or ultrafine (107 µg/m3) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated.

The availability of molecular and genetic tools has made the mouse the most common animal model for a variety of human diseases in toxicology studies. However, little is known about the factors that will influence the dose delivery to murine lungs during an inhalation study. Among these factors are the respiratory tract anatomy, lung physiology, and clearance characteristics. Therefore, the objective of this paper is to briefly review the current knowledge on the aforementioned factors in mice and their implications to the dose delivered to mouse models during inhalation studies. Representative scientific publications were chosen from searches using the NCBI PubMed and ISI Web of Knowledge databases. Relevant respiratory physiological differences have been widely reported for different mouse strains and sexes. The limited data on anatomical morphometry that is available for the murine respiratory tract indicates significant differences between mouse strains. These differences have implications to the dose delivered and the biological outcomes of inhalation studies.

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.

The availability of molecular and genetic tools has made the mouse the most common animal model for a variety of human diseases in toxicology studies. However, little is known about the factors that will influence the dose delivery to murine lungs during an inhalation study. Among these factors are the respiratory tract anatomy, lung physiology, and clearance characteristics. Therefore, the objective of this paper is to briefly review the current knowledge on the aforementioned factors in mice and their implications to the dose delivered to mouse models during inhalation studies. Representative scientific publications were chosen from searches using the NCBI PubMed and ISI Web of Knowledge databases. Relevant respiratory physiological differences have been widely reported for different mouse strains and sexes. The limited data on anatomical morphometry that is available for the murine respiratory tract indicates significant differences between mouse strains. These differences have implications to the dose delivered and the biological outcomes of inhalation studies.

Exposure to ambient particulate matter (PM) significantly increases cardiovascular morbidity and mortality in the general population. We hypothesized that some components of PM can affect the gene expression patterns in the hearts of rats exposed for 3 months to filtered air (FA), coarse (CP; 2.51.5 (for both up-and down-regulated genes), we found three genes in the CP and nine genes in the UFP groups with significantly changed expression, compared with FA. No significant changes in gene expression patterns were observed in the FP group. In the UFP group thioredoxin interacting protein (Txnip), a negative regulator of an antioxidant enzyme thioredoxin, and cytochrome P450 (Cyp2e1), an enzyme involved in the metabolism of foreign substances demonstrated significant up-regulation (fold ratios 1.79 and 1.57, respectively, with false discovery rate, FDR<0.05). In the CP group there was also a trend towards increased Txnip expression (fold ratio 1.43, FDR>0.05) and significant increase in the Cyp2e1 expression (fold ratio 1.79, FDR<0.05). Changes in the Txnip and Cyp2e1 expression showed statistically significant positive correlation to each other (p<0.0009) and were confirmed by real-time PCR. In addition Txnip and Cyp2e1 expression demonstrated statistically significant moderate correlation with the levels of MDA in the heart. Upregulation of both Cyp2e1 and Txnip are observed in hearts of patients with certain cardiac diseases. Therefore, chronic exposure to CP and UFP directly affects expression of disease-relevant genes in the myocardium.

Exposure to ambient particulate matter (PM) is linked to increases in cardiovascular morbidity and mortality. The exact mechanism by which PM induces cardiovascular toxicity is not completely understood. We sought to study histopathological changes in the heart muscle in young healthy (Wistar-Kyoto, WKY) and spontaneously hypertensive (SHR) rats and old (22-month-old) SpragueDawley rats (SD) chronically exposed to PM. WKY rats and SHR were exposed for 3 months to ultrafine particles (UFP) or filtered air (FA). SD rats were exposed for 9 months to coarse (CP), fine (FP), and ultrafine particles or FA. In addition, we studied effects of PM on mean arterial blood pressure (MABP) and echocardiograms in WKY rats and SHR. Chronic exposure to PM caused histopathological changes in the hearts of all studied strains. The effects ranged from cardiac inflammation caused by 3 months of exposure to UFP in WKY rats and SHR to more severe changes in SD rats exposed to PM for 9 months. Changes in SD rats were inflammation, intracellular edema, and vacuolization in hearts exposed to FP and UFP and vacuolization and collagen accumulation in CP-exposed hearts. In addition, evidence of only mild inflammation was seen in the respiratory tract. We did not observe any statistically significant changes in the MABP (constantly recorded over the entire period of exposure by implanted telemetric devices) and in the echocardiograms in WKY rats and SHR exposed to UFP or FA. MABP at the end of 3 months exposure comprised 153.3±13.9 and 160.3± 14.7 mmHg in the SHR-FA and SHR-UFP, respectively, and 124.4±11.2 and 107.9±9.2 mmHg in the WKY-FA and WKY-UFP, respectively (mean±SD). Our data indicate that chronic exposure to particulate air pollutants causes histopathological changes in healthy (WKY), diseased (SHR), and old SD rat hearts.

Introduction:The COVID-19 pandemic caused significant changes in delivery of healthcare. Telemedicine emerged as a popular option. Numerous studies demonstrate a favorable opinion of telemedicine from patient and physician perspectives. What factors make it more efficient and effective? This study explores how type of office visit impacts attitudes towards telemedicine and affects patient's preferences for future visits. Methods: Surveys were delivered by mail or in person to 1,100 randomly selected patients of Sierra Nevada Gastroenterology, a community-based practice in Grass Valley, CA. Each patient (pt) had a telemedicine visit (TMV) from April 2020-October 2021. Three hundred twenty surveys were returned completed. Surveys contained a 5-point Likert scale set of questions rating the quality, communication, compassion, thoroughness and convenience of TMV. In person visits (IPV) were then directly compared to TMV for the same qualities. Demographics were recorded (Table 1). Surveys were separated into 3 categories based on type of visit: new complaint (NC), follow-up of existing problem (FU), procedure-related visit (PRV). Statistical analysis and chi-square test were used to determine statistical significance. Results: Quality, communication, thoroughness and compassion during TMV rated high with Likert scores of 4.3-4.7 (5 5 strongly agree) for all groups. Comparing the 3 groups (NC, FU, PRV) with chi-square testing, no statistical difference in ratings was seen. FU pts had the highest Likert scores in all categories. Pts with new complaints preferred IPV over TMV for quality, communication, thoroughness and compassion, which was rated statistically significantly higher (P , 0.05). TMV was favored for convenience in all groups with highest ranking in FU pts (73%). Conclusion: This study showed type of office visit did not affect satisfaction or ratings of TMV. However, type of visit did reveal preferences for either IPV or TMV. Pts with NC preferred IPV and felt compassion is important and delivered more effectively in person. This suggests non-verbal communication such as body language, facial expression and tone is conveyed more effectively in person than over phone or video calls. FU or PRV pts rated TMV as more convenient and preferable over IPV for future visits, suggesting that pts with stable or less acute problems prioritize convenience over other factors when selecting type of visit. Further studies are needed to determine what other factors will influence and improve quality of TMV.