Final Exposure Research Articles

Evaluation of learning and exposure in the undergraduate interventional radiology curriculum (ELIXIR)

To gauge current final year medical students' exposure to interventional radiology (IR)and assess their perceptions of IR as a prospective career option. An online questionnaire comprising of questions that gauge final-year medical students' understanding of and exposure to IR based on the recommendations set out by the British Society of Interventional Radiology (BSIR), was sent out to final-year students across 34 UK medical schools. Five hundred and ten responses were collected from 33 out of 34 eligible medical schools. Sixty-four per cent of respondents rated their own IR knowledge as inadequate. On average, only 50% of all subtopics proposed in the BSIR undergraduate curriculum was covered during medical school and 32.7% of respondents were not exposed to any fundamental IR principles and techniques recommended by the BSIR during medical school. Regarding careers, 2.7% of respondents reported a definite interest in pursuing a career in IR. Most respondents (89.8%) felt that there was insufficient undergraduate teaching on IR and that they lacked information to consider pursuing a career in IR (87.5%). Insufficient exposure and teaching on IR throughout medical schools have led to a lack of awareness and consideration of IR as a future career choice amongst UK medical students. The re-evaluation of IR teaching in the medical school curricula is needed. In the long-term, such recommendations could provide the much-needed solution to the workforce shortages seen in IR.

Genetic algorithm-based optical proximity correction for DMD maskless lithography.

We present an optical proximity correction (OPC) method based on a genetic algorithm for reducing the optical proximity effect-induced pattern distortion in digital micromirror device (DMD) maskless lithography. Via this algorithm-assisted grayscale modulation of the initial mask at the pixel level, the exposure pattern can be enhanced significantly. Actual exposure experiments revealed that the rate of matching between the final exposure pattern and the mask pattern can be increased by up to 20%. This method's applicability to complex masks further demonstrates its universality for mask pattern optimization. We believe that our algorithm-assisted OPC could be highly helpful for high-fidelity and efficient DMD maskless lithography for microfabrication.

Hyperbaric air mobilizes stem cells in humans; a new perspective on the hormetic dose curve.

Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund "Spanish flu pandemic" patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been completely displaced by 100% oxygen to create the modern pharmaceutical hyperbaric oxygen therapy (HBOT), a powerful treatment that is FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count. Ten 34-35-year-old healthy volunteers were exposed to 1.27ATA (4 psig/965 mmHg) room air for 90 min, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: (1) prior to the first exposure (served as the control for each subject), (2) directly after the first exposure (to measure the acute effect), (3) immediately prior to the ninth exposure (to measure the chronic effect), and (4) 3 days after the completion of tenth/final exposure (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry. SPCs (CD45dim/CD34+/CD133-) were mobilized by nearly two-fold following 9 exposures (p = 0.02) increasing to three-fold 72-h post completion of the final (10th) exposure (p = 0.008) confirming durability. This research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated to reflect a dose treatment finding rather than finding a placebo effect. Our findings of SPC mobilization by HBA support further investigation into hyperbaric air as a pharmaceutical/therapy.

Wildfire-related smoke inhalation worsens cardiovascular risk in sleep disrupted rats.

As a lifestyle factor, poor sleep status is associated with increased cardiovascular morbidity and mortality and may be influenced by environmental stressors, including air pollution. To determine whether exposure to air pollution modified cardiovascular effects of sleep disruption, we evaluated the effects of single or repeated (twice/wk for 4 wks) inhalation exposure to eucalyptus wood smoke (ES; 964 μg/m3 for 1 h), a key wildland fire air pollution source, on mild sleep loss in the form of gentle handling in rats. Blood pressure (BP) radiotelemetry and echocardiography were evaluated along with assessments of lung and systemic inflammation, cardiac and hypothalamic gene expression, and heart rate variability (HRV), a measure of cardiac autonomic tone. GH alone disrupted sleep, as evidenced by active period-like locomotor activity, and increases in BP, heart rate (HR), and hypothalamic expression of the circadian gene Per2. A single bout of sleep disruption and ES, but neither alone, increased HR and BP as rats transitioned into their active period, a period aligned with a critical early morning window for stroke risk in humans. These responses were immediately preceded by reduced HRV, indicating increased cardiac sympathetic tone. In addition, only sleep disrupted rats exposed to ES had increased HR and BP during the final sleep disruption period. These rats also had increased cardiac output and cardiac expression of genes related to adrenergic function, and regulation of vasoconstriction and systemic blood pressure one day after final ES exposure. There was little evidence of lung or systemic inflammation, except for increases in serum LDL cholesterol and alanine aminotransferase. These results suggest that inhaled air pollution increases sleep perturbation-related cardiovascular risk, potentially in part by increased sympathetic activity.

Associations of prenatal exposure to NO2 and near roadway residence with placental gene expression

IntroductionTraffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression. MethodsWhole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO2 exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO2 or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10). ResultsIn GAPPS, final-month NO2 exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO2 on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO2 on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants). DiscussionOverall, pregnancy NO2 exposure and placental gene expression associations were primarily null, with exception of final month NO2 exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2, CEBPA, and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation.

Protective effect of Securiniga suffruticosa on Diesel vehicles-derived PM2.5 induces lung and cardiovascular injury

Respiratory exposure to Particulate Matter (PM), including Diesel exhaust particulate (DEP), causes oxidative stress-induced lung inflammation. Especially, fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) is a serious air pollutant associated with various health problems. DEP and PM2.5 pollutants in the air are enter into pulmonary and even bloodstream, and can be causes of inflammatory disorders that are related with respiratory response. The present study aimed to examine the inhibitory effect of Securiniga suffruticosa (S. suffruiticosa) on DEP-induced lung and cardiovascular diseases. The mice groups are follows; sham group: C57BL6 male mice, DEP group: C57BL6 male mice inhaled DEP, S. suffruiticosa Low group: DEP + 100 mg/kg/day S. suffruiticosa, and S. suffruiticosa High group: DEP + 300 mg/kg/day S. suffruiticosa. Mice inhaled DEP by using nebulizer chamber and were sacrificed 48 hours after final exposure of DEP. Treatment with S. suffruiticosa reduced the expression of inducible CXCL1 and CXCL2 in bronchoalveolar lavage fluid and Muc5ac, ICAM-1, TNF-α, IL-6 mRNA in lung were also attenuated by S. suffruiticosa. In thoracic aorta, DEP increased CAMs, TNF-α and inflammasome markers such as NLRP3, Caspase-1, and ASC. However, S. suffruiticosa suppressed these levels. In HUVECs, S. suffruiticosa inhibited PM2.5 induced production of intracellular reactive oxygen species (ROS); and inhibited the translocation of NF-κB p65 to the nucleus in HUVECs (human umbilical vein endothelial cells). Taken together, this study proved that exposure to PM2.5 induced both lung and vascular inflammation, however, S. suffruiticosa attenuated this injury via the downregulation of the NLRP3 signaling pathway. These findings suggest that S. suffruiticosa may have potential therapeutic benefit against air pollution-mediated lung and cardiovascular diseases. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2021R1I1A1A01056937). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

No detectable changes in anxiety-related and locomotor behaviors in adult ovariectomized female rats exposed to estradiol, the ERβ agonist DPN or the ERα agonist PPT

The sex steroid hormone 17β-estradiol (estradiol) and its Estrogen Receptors (ERs) have been linked to modulation of anxiety-related and locomotor behaviors in female rodents. Research suggests that estradiol mitigates anxiety-related behaviors through activating Estrogen Receptor (ER)β and increases locomotor behaviors through ERα. The influence of ERs on these behaviors cannot always be detected. Here we discuss two experiments in which we tested the hypothesis that anxiety-related behaviors would decrease after ERβ activation and locomotor behaviors would increase after ERα activation, and also assessed the persistence of these behavioral effects by varying the timing of behavioral testing. Two cohorts of adult female ovariectomized rats were exposed to estradiol, the ERβ agonist DPN, the ERα agonist PPT, or oil for four consecutive days. Body mass was assessed throughout as a positive control. In both cohorts, open field behaviors were assessed on the first day of exposure. In one cohort (Experiment 1), open field, light/dark box, and elevated plus maze behaviors were assessed on the final day of injections. In the second cohort (Experiment 2), these behaviors were assessed 24 h after the final exposure. As expected, significant differences in body mass were detected in response to estradiol and PPT exposure, validating the estradiol and ER manipulation. No significant differences were observed in anxiety-related or locomotor behaviors across treatment groups, indicating that the efficacy of these agonists as therapeutic agents may be limited. We review these results in the context of previous literature, emphasizing relevant variables that may obscure ER-related actions on behavior.

Compact ultraviolet light-emitting diode-based lithography illumination system with tunable coherent factor

Optimization of the illumination system of an ultraviolet light-emitting diode (UVLED)-based lithography system by reducing the system complexity and spatial volume has been a research focus. This work proposes a compact lithography illumination system that applies a specially designed embedded compound parabolic concentrator (ECPC) to replace the traditional collimation module and the zoom lenses module. The ECPC, comprised of two detachable parabolic surfaces, precisely collimates all light beams from the UVLED to a preset divergence angle of 6 deg and provides an adjustable lithography coherent factor. The final illumination system offers a square illumination field with a uniformity of up to 1.3% in the large coherent factor and a linearly adjustable numerical aperture in the range of 0.02 ∼ 0.04. The final exposure result of 0.7 μm based on the experiment setup further verifies the performance of the designed illumination system.

Queer Narratives in Nordic Sami Literature: Coming-Out Narratives and Final Exposures in Savior of the Lost Children (2008) and Himlabrand (2021)

ABSTRACT This article explores how two queer narratives in Nordic Sami literature challenge, expand and change norms and stereotypes related to queer indigenous experiences. Characteristic for these narratives is the ambition to highlight taboos and challenge stereotypes in Sami contexts. In the article, I explore the characters’ coming-out processes and relate them to larger narrative traditions. To shed light on the obstacles the characters meet in the process of coming out to themselves and to their communities, and the genres through which the stories are told, I turn to gender scholars Judith Roof, Andrea Gutenberg and Anne Mulhall. I make use of their perspectives to explore whether the coming-out processes take different shapes when the individuals in question are Sami and thus doubly minoritized. Insisting on the importance of coming out not only to oneself, but also to the Sami community at large, they take on an important activist role, transcending the perspective of the individual. The primary texts are the young-adult novel Himlabrand (“Heavenly fire”) (2021) by Moa Backe Åstot and the blog novel The Savior of the Lost Children (2008) by Sigbjørn Skåden.

Enhancement of pattern quality in maskless plasmonic lithography via spatial loss modulation

Plasmonic lithography, which uses the evanescent electromagnetic (EM) fields to generate image beyond the diffraction limit, has been successfully demonstrated as an alternative lithographic technology for creating sub-10 nm patterns. However, the obtained photoresist pattern contour in general exhibits a very poor fidelity due to the near-field optical proximity effect (OPE), which is far below the minimum requirement for nanofabrication. Understanding the near-field OPE formation mechanism is important to minimize its impact on nanodevice fabrication and improve its lithographic performance. In this work, a point-spread function (PSF) generated by a plasmonic bowtie-shaped nanoaperture (BNA) is employed to quantify the photon-beam deposited energy in the near-field patterning process. The achievable resolution of plasmonic lithography has successfully been enhanced to approximately 4 nm with numerical simulations. A field enhancement factor (F) as a function of gap size is defined to quantitatively evaluate the strong near-field enhancement effect excited by a plasmonic BNA, which also reveals that the high enhancement of the evanescent field is due to the strong resonant coupling between the plasmonic waveguide and the surface plasmon waves (SPWs). However, based on an investigation of the physical origin of the near-field OPE, and the theoretical calculations and simulation results indicate that the evanescent-field-induced rapid loss of high-k information is one of the main optical contributors to the near-field OPE. Furthermore, an analytic formula is introduced to quantitatively analyze the effect of the rapidly decaying feature of the evanescent field on the final exposure pattern profile. Notably, a fast and effective optimization method based on the compensation principle of the exposure dose is proposed to reduce the pattern distortion by modulating the exposure map with dose leveling. The proposed pattern quality enhancement method can open new possibilities in the manufacture of nanostructures with ultrahigh pattern quality via plasmonic lithography, which would find potentially promising applications in high density optical storage, biosensors, and plasmonic nanofocusing.

Persisting Cryptococcus yeastspecies Vishniacozyma victoriae and Cryptococcus neoformans elicit unique airway inflammation in mice following repeated exposure.

Allergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as Cryptococcus neoformans are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including Vishniacozyma victoriae (syn. Cryptococcus victoriae), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated V. victoriae exposure was previously unexplored. This study aimed to compare the immunological impact of repeated pulmonary exposure to Cryptococcus yeasts. Mice were repeatedly exposed to an immunogenic dose of C. neoformans or V. victoriae via oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected to examine airway remodeling, inflammation, mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to C. neoformans and V. victoriae were analyzed and compared. Following repeated exposure, both C. neoformans and V. victoriae cells were still detectable in the lungs 21 days post final exposure. Repeated C. neoformans exposure initiated myeloid and lymphoid cellular infiltration into the lung that worsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated V. victoriae exposure induced a strong CD4+ T cell-driven lymphoid response that started to resolve by 21 days post final exposure. C. neoformans remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of V. victoriae in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of V. victoriae, these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD.

Salvianolic Acid B Regulates Oxidative Stress, Autophagy and Apoptosis against Cyclophosphamide-Induced Hepatic Injury in Nile Tilapia (Oreochromis niloticus).

Salvianolic acid B (Sal B), as one of the main water-soluble components of Salvia miltiorrhizae, has significant pharmacological activities, including antioxidant, free radical elimination and biofilm protection actions. However, the protective effect of Sal B on Nile tilapia and the underlying mechanism are rarely reported. Therefore, the aim of this study was to evaluate the effects of Sal B on antioxidant stress, apoptosis and autophagy in Nile tilapia liver. In this experiment, Nile tilapia were fed diets containing sal B (0.25, 0.50 and 0.75 g·kg-1) for 60 days, and then the oxidative hepatic injury of the tilapia was induced via intrapleural injection of 50 g·kg-1 cyclophosphamide (CTX) three times. After the final exposure to CTX, the Nile tilapia were weighed and blood and liver samples were collected for the detection of growth and biochemical indicators, pathological observations and TUNEL detection, as well as the determination of mRNA expression levels. The results showed that after the CTX treatment, the liver was severely damaged, the antioxidant capacity of the Nile tilapia was significantly decreased and the hepatocyte autophagy and apoptosis levels were significantly increased. Meanwhile, dietary Sal B can not only significantly improve the growth performance of tilapia and effectively reduce CTX-induced liver morphological lesions, but can also alleviate CTX-induced hepatocyte autophagy and apoptosis. In addition, Sal B also significantly regulated the expression of genes related to antioxidative stress, autophagy and apoptosis pathways. This suggested that the hepatoprotective effect of Sal B may be achieved through various pathways, including scavenging free radicals and inhibiting hepatocyte apoptosis and autophagy.

Clinical case series: Botulinum toxin and the reversible correction of gingival smile

The aim of this study was to evaluate the effect of applying botulinum toxin type A (BTX-A) as a therapeutic alternative for the treatment of gingival smile. Four selected categories of female gender, aged 28–38 years, with gingival smile exposure between 4 and 9 mm, were selected. The evaluation was carried out 15 and 30 days after the initial application. All participants responded to a structured scored interview of initial and final satisfaction. All patients related satisfaction with the final gingival exposure, providing an improvement of their self-esteem. The gingival smile can be treated with botulinum toxin type A as an adjunct to treatments that involve ortho-surgical facial rehabilitation. Although the result is completely reversed after a complete elimination of the product, it can improve the patient’s self-esteem. More clinical trials are important to confirm the results

Observational prospective unblinded case-control study to evaluate the effect of the Gamma3® distal targeting system for long nails on radiation exposure and time for distal screw placement

PurposeTo determine if the DTS decreases radiation exposure (primary outcome measure), fluoroscopy time (secondary outcome measure), and time to distal screw placement (secondary outcome measure) compared to the freehand “perfect circles” method when used for locking of cephalomedullary nails in the treatment of femur fractures MethodsFifty-eight patients with hip or femoral shaft fractures that were treated with a long cephalomedullary nail were enrolled in this study. Cohorts were determined based on the method of distal interlocking screw placement into either the “Perfect Circles” or “Distal Targeting” cohort. Time from cephalad screw placement to placement of final distal interlocking screw (seconds), radiation exposure (mGy), and fluoroscopy time (seconds) were compared between groups. Hospital quality measures were compared between cohorts. ResultsUse of the DTS resulted in 77% (4.3x) lower radiation exposure (p < 0.001), 64% (2.7x) lower fluoroscopy time (p < 0.001), and 60% (1.7x) lower intraoperative time from end of cephalad screw placement to end of distal interlocking screw placement (p < 0.001) compared to the freehand “perfect circles” method. There was no difference in 30-day or 90-day complication rates between cohorts. ConclusionThe Stryker Gamma3® Distal Targeting System is a safe, effective and efficient alternative to the freehand “perfect circles” method.

Estrous cycle and hormone regulation of stress-induced reinstatement of reward seeking in female mice

Women are more vulnerable to stress-induced craving, which may be associated with increased vulnerability to relapse. Susceptibility to stress-induced craving also appears to be modulated by the menstrual cycle and is negatively correlated with circulating progesterone levels in women. However, the factors that contribute to relapse vulnerability are poorly characterized in female animals. In this study, we assessed whether chronic ethanol exposure, estrous cycle, or exogenous progesterone administration modulated vulnerability to stress-induced reinstatement. To model ethanol dependence, adult female C57Bl/6J mice underwent chronic intermittent ethanol (CIE) exposure via vapor inhalation. Seventy-two hours after the final ethanol exposure, food-restricted mice began training in a conditioned place preference paradigm (CPP) for a food reward, followed by extinction training. Mice were then subjected to forced swim stress and assessed for reinstatement of their preference for the reward-paired chamber. CIE did not affect stress-induced reinstatement. However, stress-induced reinstatement was attenuated during the diestrus phase, when endogenous levels of progesterone peak in female mice. Further, administration of exogenous progesterone mimicked the attenuated reinstatement observed in diestrus. These findings indicate that circulating hormone levels modulate susceptibility to relapse-like behaviors and implicate progesterone as a potential target for treating stress-induced relapse in women.

Inhibition of methylmercury uptake by freshwater phytoplankton in presence of algae-derived organic matter

As the first step of methylmercury (MeHg) entry into the aquatic food webs, MeHg uptake by phytoplankton is crucial in determining the final human MeHg exposure risks. MeHg availability to plankton is regulated by dissolved organic matter (DOM) in the water, while the extent of the impacts can vary largely based on the sources of DOM. Here, we investigated impacts of DOM sources on MeHg bioconcentration by three freshwater phytoplankton species (i.e. S. quadricauda, Chlorella sp., Microcystis elabens) in the laboratory system. We found that algae-derived DOM would prohibited the cellular MeHg bioconcentration by a percent up to 77–93%, while the soil-derived DOM didn't show similar inhibition effects. DOM characterization by the excitation‒emission matrices, Fourier transform infrared spectrum, ultra‒high performance liquid chromatography‒tandem quadrupole time of flight mass spectrometry shown that the molecular size of S-containing compound, rather than thiol concentration, has played a crucial role in regulating the MeHg uptake by phytoplankton. Climate change and increasing nutrient loadings from human activities may affect plankton growth in the freshwater, ultimately changing the DOM compositions. Impacts of these changes on cellular MeHg uptakes by phytoplankton should be emphasized when exploring the aquatic Hg cycling and evaluating their risks to human beings and wild life.

Activation of plant immunity by exposure to dinitrogen pentoxide gas generated from air using plasma technology.

Reactive nitrogen species (RNS) play an important role in plant immunity as signaling factors. We previously developed a plasma technology to partially convert air molecules into dinitrogen pentoxide (N2O5), an RNS whose physiological action is poorly understood. To reveal the function of N2O5 gas in plant immunity, Arabidopsis thaliana was exposed to plasma-generated N2O5 gas once (20 s) per day for 3 days, and inoculated with Botrytis cinerea, Pseudomonas syringae pv. tomato DC3000 (Pst), or cucumber mosaic virus strain yellow (CMV(Y)) at 24 h after the final N2O5 gas exposure. Lesion size with B. cinerea infection was significantly (P < 0.05) reduced by exposure to N2O5 gas. Propagation of CMV(Y) was suppressed in plants exposed to N2O5 gas compared with plants exposed to the air control. However, proliferation of Pst in the N2O5-gas-exposed plants was almost the same as in the air control plants. These results suggested that N2O5 gas exposure could control plant disease depending on the type of pathogen. Furthermore, changes in gene expression at 24 h after the final N2O5 gas exposure were analyzed by RNA-Seq. Based on the gene ontology analysis, jasmonic acid and ethylene signaling pathways were activated by exposure of Arabidopsis plants to N2O5 gas. A time course experiment with qRT-PCR revealed that the mRNA expression of the transcription factor genes, WRKY25, WRKY26, WRKY33, and genes for tryptophan metabolic enzymes, CYP71A12, CYP71A13, PEN2, and PAD3, was transiently induced by exposure to N2O5 gas once for 20 s peaking at 1–3 h post-exposure. However, the expression of PDF1.2 was enhanced beginning from 6 h after exposure and its high expression was maintained until 24–48 h later. Thus, enhanced tryptophan metabolism leading to the synthesis of antimicrobial substances such as camalexin and antimicrobial peptides might have contributed to the N2O5-gas-induced disease resistance.

Inhibition of Serum Esterases in Juvenile Rats Repeatedly Exposed to Low Levels of Chlorpyrifos.

Chlorpyrifos (CPF) is an organophosphorus insecticide that has gained significant attention cue to the reported toxicity associated with developmental exposure. While the canonical mechanism of toxicity of CPF involves the inhibition of brain acetylcholinesterase (AChE), we have reported that exposure of juvenile rats to levels of CPF that do not yield any inhibition of brain AChE results in neurobehavioral alterations at later ages. However, it is unclear what effect exposure to these low levels of CPF has on blood esterase activities which are frequently used not only as biomarkers of exposure but also to set exposure levels in risk assessment. To determine this, male and female rat pups were exposed orally from postnatal day 10 to 16 to either corn oil (vehicle) or 0.5, 0.75, or 1.0 mg/kg CPF. At 12 h after the final exposure, serum cholinesterase (ChE), butyrylcholinesterase (BChE), and carboxylesterase (CES), and red blood cell (RBC) and brain AChE activities were determined. There were no differences between sexes in either the controls or individual treatments for all enzymes. Only the highest dosage of 1.0 mg/kg CPF yielded significant brain AChE inhibition (22-24%) but all dosages significantly inhibited the blood esterases with inhibition being highest with serum CES (65-85%) followed by serum BChE (57-76%), RBC AChE (35-65%), and then serum ChE (16-32%). Our data verify that blood esterases are inhibited at dosages of CPF that alter neurobehavioral performance in the absence of effects on brain AChE activity.

Exposure to Vishniacozyma victoriae elicits airway inflammation and a CD4+ T cell-driven lymphocytic response.

Abstract Like the pathogenic yeast Cryptococcus neoformans, Vishniacozyma victoriae (syn. Cryptococcus victoriae), a non-pathogenic yeast, has been associated with allergic airway disease. Although V. victoriae is frequently detected in indoor environments, the impact of repeated exposure is currently unknown. In this study, mice were exposed via oropharyngeal aspiration to V. victoriae or C. neoformans every other day for a total of six exposures, and responses were analyzed 1 day and 21 days post final exposure. As expected, repeated exposure to C. neoformans resulted in an increase of myeloid and lymphoid cells in the bronchoalveolar lavage fluid (BALF), granuloma formation with intralesional yeast, and peribronchiolar and perivascular inflammation 1 day post exposure. This response was exacerbated 21 days post exposure as the yeast cells replicated. Repeated exposure to V. victoriae resulted in an increase in eosinophils, Ly6Chi/int monocytes, and CD103+ dendritic cells in the BALF, and mild perivascular and peribronchiolar inflammation 1 day post exposure. Surprisingly, V. victoriae cells were present in the lungs of exposed mice 21 days post exposure, and the response shifted toward a nodular lymphocytic response with an increase of CD4+ T cells in the BALF. Lastly, C. neoformans exposure was predicted to activate antigen presentation, B cell development and Th2 proteomic pathways, whereas V. victoriae was predicted to activate VDR/RXR activation, Granzyme A signaling, and IGF-1 signaling pathways 21 days post exposure. The results of this study suggest that exposure to environmentally ubiquitous V. victoriae may exacerbate allergic airway disease, although not to the extent of exposure to pathogenic C. neoformans. Interagency Agreement between NIEHS &amp; NIOSH: AES 12007001-1-0-6

Head and neck cancer and asbestos exposure

ObjectivesThe aim of this study was to analyse, within a French cohort of workers previously occupationally exposed to asbestos, incidence and mortality from various sites of head and neck cancers...