Examination of the exposome in an animal model: The impact of high fat diet and rat strain on local and systemic immune markers following occupational welding fume exposure.

The goal of this study was to investigate the impact of multiple exposomal factors (genetics, lifestyle factors, environmental/occupational exposures) on pulmonary inflammation and corresponding alterations in local/systemic immune parameters. Accordingly, male Sprague-Dawley (SD) and Brown Norway (BN) rats were maintained on either regular (Reg) or high fat (HF) diets for 24wk. Welding fume (WF) exposure (inhalation) occurred between 7 and 12wk. Rats were euthanized at 7, 12, and 24wk to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7wk, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality)-effects which were more pronounced in SD rats. Indices of lung injury/inflammation were elevated in all WF-exposed animals at 12wk; however, diet appeared to preferentially impact SD rats at this time point, as several inflammatory markers (lymph node cellularity, lung neutrophils) were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery by 24wk. In BN rats, resolution of immune alterations was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24wk. Collectively, HF diet appeared to have a greater impact on global immune status and exposure-induced lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the combined impact of genetic, lifestyle, and environmental factors in modulating immunological responsivity and emphasize the importance of the exposome in shaping biological responses.

Effects of whole-body vibration on reproductive physiology in a rat model of whole-body vibration.

Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.

County-level demographic, social, economic, and lifestyle correlates of COVID-19 infection and death trajectories during the first wave of the pandemic in the United States.

BACKGROUND: The US COVID-19 epidemic impacted counties differently across space and time, though large-scale transmission dynamics are unclear. The study's objective was to group counties with similar trajectories of COVID-19 cases and deaths and identify county-level correlates of the distinct trajectory groups. METHODS: Daily COVID-19 cases and deaths were obtained from 3141 US counties from January through June 2020. Clusters of epidemic curve trajectories of COVID-19 cases and deaths per 100,000 people were identified with Proc Traj. We utilized polytomous logistic regression to estimate Odds Ratios for trajectory group membership in relation to county-level demographics, socioeconomic factors, school enrollment, employment and lifestyle data. RESULTS: Six COVID-19 case trajectory groups and five death trajectory groups were identified. Younger counties, counties with a greater proportion of females, Black and Hispanic populations, and greater employment in private sectors had higher odds of being in worse case and death trajectories. Percentage of counties enrolled in grades 1-8 was associated with earlier-start case trajectories. Counties with more educated adult populations had lower odds of being in worse case trajectories but were generally not associated with worse death trajectories. Counties with higher poverty rates, higher uninsured, and more living in non-family households had lower odds of being in worse case and death trajectories. Counties with higher smoking rates had higher odds of being in worse death trajectory counties. DISCUSSION: In the absence of clear guidelines and personal protection, smoking, racial and ethnic groups, younger populations, social, and economic factors were correlated with worse COVID-19 epidemics that may reflect population transmission dynamics during January-June 2020. After vaccination of high-risk individuals, communities with higher proportions of youth, communities of color, smokers, and workers in healthcare, service and goods industries can reduce viral spread by targeting vaccination programs to these populations and increasing access and education on non-pharmaceutical interventions.

Inhalation of iron-abundant gas metal arc welding-mild steel fume promotes lung tumors in mice.

Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 µg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer.

Increased susceptibility of hyperthyroid rats to ozone: early events and mechanisms.

Previous studies demonstrated that ozone-induced lung damage and inflammation are much greater in hyperthyroid rats, compared to normal rats, at 18 h postexposure. The purpose of the present investigation was to study early events and mechanisms underlying the increased sensitivity to ozone in a hyperthyroid state. Specifically, the degree of lung epithelial cell barrier disruption, the antioxidant status of the extracellular lining fluid, and the release of inflammatory mediators were examined. To induce a hyperthyroid state, mature male Sprague-Dawley rats were implanted with time-release pellets containing thyroxine; control rats received placebo pellets. After 7 d, the animals were exposed to air or ozone (2 ppm, 3 h). Immediately following the end of the exposure, bronchoalveolar lavage (BAL) fluid and cells were harvested. BAL fluid albumin levels and total antioxidant status were examined. In addition, levels of prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-2, MCP-1, and tumor necrosis factor (TNF)-alpha were determined in BAL fluid and in media samples following ex vivo culture of BAL cells harvested after in vivo inhalation exposures. The results of this study are consistent with the following hypotheses: (1) A marked increase in the permeability of the alveolar-capillary barrier is an early event following ozone exposure in a hyperthyroid state; however this does not appear to be due to overall changes in BAL fluid antioxidant potential. (2) Early increases in MIP-2, but not PGE2, are involved in the enhanced lung response to ozone in a hyperthyroid state. (3) Inflammatory mediator production (i.e., PGE2, MIP-2, MCP-1, and TNF-alpha) by alveolar macrophages plays a minimal role in the initial responses to ozone in a hyperthyroid state.

Very High Power THz Radiation Sources.

We report the production of high power (20watts average, ∼ 1 Megawatt peak) broadbandTHz light based on coherent emission fromrelativistic electrons. Such sources areideal for imaging, for high power damagestudies and for studies of non-linearphenomena in this spectral range. Wedescribe the source, presenting theoreticalcalculations and their experimentalverification. For clarity we compare thissource with one based on ultrafast lasertechniques.

Observation of broadband self-amplified spontaneous coherent terahertz synchrotron radiation in a storage ring.

Bursts of coherent synchrotron radiation at far-infrared and millimeter wavelengths have been observed at several storage rings. A microbunching instability has been proposed as the source for the bursts. However, the microbunching mechanism has yet to be elucidated. We provide the first evidence that the bursts are due to a microbunching instability driven by the emission of synchrotron radiation in the bunch. Observations made at the Advanced Light Source are consistent with the values predicted by the proposed microbunching model. These results demonstrate a new instability regime for high energy synchrotron radiation sources and could impact the design of future sources.

Adverse cardiac events after surgery: assessing risk in a veteran population.

OBJECTIVE: To establish rates of and risk factors for cardiac complications after noncardiac surgery in veterans. DESIGN: Prospective cohort study. SETTING: A large urban veterans affairs hospital. PARTICIPANTS: One thousand patients with known or suspected cardiac problems undergoing 1,121 noncardiac procedures. MEASUREMENTS: Patients were assessed preoperatively for important clinical variables. Postoperative evaluation was done by an assessor blinded to preoperative status with a daily physical examination, electrocardiogram, and creatine kinase with MB fraction until postoperative day 6, day of discharge, death, or reoperation (whichever occurred earliest). Serial electrocardiograms, enzymes, and chest radiographs were obtained as indicated. Severe cardiac complications included cardiac death, cardiac arrest, myocardial infarction, ventricular tachycardia, and fibrillation and pulmonary edema. Serious cardiac complications included the above, heart failure, and unstable angina. MAIN RESULTS: Severe and serious complications were seen in 24% and 32% of aortic, 8.3% and 10% of carotid, 11.8% and 14.7% of peripheral vascular, 9.0% and 13.1% of intraabdominal/intrathoracic, 2.9% and 3.3% of intermediate-risk (head and neck and major orthopedic procedures), and 0.27% and 1.1% of low-risk procedures respectively. The five associated patient-specific risk factors identified by logistic regression are: myocardial infarction < 6 months (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.9 to 12.9), emergency surgery (OR, 2.6; 95% CI, 1.2 to 5.6), myocardial infarction > 6 months (OR, 2.2; 95% CI, 1.4 to 3.5), heart failure ever (OR, 1.9; 95% CI, 1.2 to 3.0), and rhythm other than sinus (OR, 1.7; 95% CI, 0.9 to 3.2). Inclusion of the planned operative procedure significantly improves the predictive ability of our risk model. CONCLUSIONS: Five patient-specific risk factors are associated with high risk for cardiac complications in the perioperative period of noncardiac surgery in veterans. Inclusion of the operative procedure significantly improves the predictive ability of the risk model. Overall cardiac complication rates (pretest probabilities) are established for these patients. A simple nomogram is presented for calculation of post-test probabilities by incorporating the operative procedure.

The successful surgical treatment of a paradoxical embolus to the carotid bifurcation.

Paradoxical embolism is a rare cause of ischemic stroke. We report the case of a 67-year-old man who had a saddle embolus to the carotid bifurcation successfully treated with emergency embolectomy. Transesophageal echocardiogram revealed a large patent foramen ovale and an easily demonstrable right-to-left shunt. Subsequent investigations revealed proximal deep venous thrombosis in the left femoral and popliteal veins and multiple pulmonary emboli. Long-term anticoagulation was instituted for the diagnosis of paradoxical embolism. The patient's recovery was uneventful, and he remained neurologically intact. A literature review emphasizes the role of transesophageal echocardiography and suggests that paradoxical embolism may be a more common cause of stroke than previously thought.

IR spectroscopic characteristics of cell cycle and cell death probed by synchrotron radiation based Fourier transform IR spectromicroscopy.

Synchrotron radiation based Fourier transform IR (SR-FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR-FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR-90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G(1)-phase to the S-phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl C===O peak at 1743 cm(-1) is observed. Biopolymers (Biospectroscopy) 57: 329-335, 2000

Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro.

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P

Pharmacist recognition of potential drug interactions.

The ability of pharmacists to identify potential drug interactions was studied. Simulated medication profiles were created from a list of 16 drugs. Staff pharmacists and soon-to-graduate student pharmacists at a Veterans Affairs medical center each received a set of eight 2-drug profiles, four 4-drug profiles, two 8-drug profiles, and one 16-drug profile. Each set of profiles contained a number of pairs of drugs rated by the Drug Therapy Screening System as producing an interaction of moderate or major importance. The subjects were given one hour to screen the profile for the potentially interacting pairs. The subjects detected only 66% of the interactions in the 2-drug profiles, 34% of the interactions in the 4-drug profiles, 20% of the interactions in the 8-drug profiles, and 17% of the interactions in the 16-drug profile. None of the subjects detected all interactions in the 8- or 16-drug profiles. Both true-positive and false-positive rates of identification decreased significantly as the number of drugs listed on the profile increased. This primarily reflected a reduced tendency to report the presence of drug interactions, but there was additional evidence that the accuracy of identification also declined. The number of years of pharmacy training was the only demographic characteristic highly correlated with accuracy. More years of pharmacy education seemed to improve the ability to detect drug interactions. However, none of the pharmacists or students was able to detect all potentially interacting pairs in a profile containing 8 or 16 drugs. Computerized drug interaction profiles should be used by pharmacists to ensure recognition of all potential drug interactions.

Cytokine mediation of ozone-induced pulmonary adaptation.

Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.

Vagus nerve imaging with ultrasound: anatomic and in vivo validation.

To provide the anatomic basis and demonstrate the reproducibility of ultrasound studies for the identification of the vagus nerve within its course in the carotid sheath in the neck, cadaveric and in vivo imaging studies were conducted. On transverse B-mode images of the neck, there is a centrally hypoechoic and peripherally hyperechoic structure between the common carotid artery and the jugular vein inside the carotid sheath. This structure was also identified in a fresh, nonpreserved cadaver and was marked with a hypodermic needle by means of a transdermal approach. Neck dissection was performed leaving the carotid sheath intact. B-mode imaging yielded detailed anatomic information about the structures in the carotid sheath. Further dissection showed the vagus nerve as the target of the needle. One hundred consecutive transverse carotid scans were reviewed, and the characteristic echo patterns of the vagus nerve were identified in 97 instances. A distinct and reproducible, round, hypoechoic structure was defined adjacent to the common carotid artery and jugular vein as the vagus nerve. On the basis of this study, a new, noninvasive, and highly reproducible method to locate the vagus nerve in the carotid sheath is introduced. This may lead to further clinical application such as presurgical localization or ultrasound-guided needle studies. Stimulation of the vagus nerve has been proposed for seizure therapy. The diagnosis of vagus nerve tumors may be improved.

Comparing the smoking behavior of veterans and nonveterans.

OBJECTIVES: The authors analyzed self-reported questionnaire data from the 1987 National Medical Expenditure Survey (NMES) to determine the smoking patterns of veterans. METHODS: Using NMES data, the authors compared veterans versus nonveterans overall, women veterans versus women nonveterans, Vietnam-era veterans versus other veterans, and veterans whose usual source of medical care was the Department of Veterans Affairs (VA) system versus veterans who received care elsewhere. RESULTS: The likelihood of ever having smoked cigarettes was higher for veterans than for nonveterans and for women veterans than for women nonveterans. The prevalence of current smoking was higher for veterans than for nonveterans and higher for those seeking care within the VA system than for other veterans. CONCLUSIONS: Given the enormous health care costs associated with smoking, health promotion efforts should be developed to reduce the high rate of smoking among veterans--especially those who are consumers of VA health care.

Educating patients with limited literacy skills: the effectiveness of printed and videotaped materials about colon cancer.

We investigated whether printed or videotaped information is more effective in enhancing colon cancer knowledge. Subjects (n = 1100) were randomized into three groups: to receive a booklet, view a videotape, or receive no intervention. Subjects receiving the intervention showed increased knowledge compared with control subjects (booklet = 23% and videotape = 26% vs no intervention = 3%). Findings suggest that personalized educational materials are effective in enhancing colon cancer knowledge.

Perioperative prophylaxis of venous thromboembolism.

Venous thromboembolism is an important cause of morbidity and mortality in hospitalized patients, causing 100,000 to 200,000 deaths per year in the United States. Patients undergoing surgery are at the highest risk of venous thromboembolism. The magnitude of this risk in a patient depends on the surgical procedure performed and the presence of other risk factors that predispose to venous thromboembolism. The clinical diagnosis of both deep vein thrombosis and pulmonary embolism is notoriously inaccurate. Furthermore, two thirds of all fatal pulmonary emboli cause death within 30 minutes of the embolic episode, leaving little time for diagnostic work-up and effective treatment. Prophylactic treatment for prevention of venous thromboembolism is therefore important in these patients, and several effective mechanical and chemical methods for this purpose are available. The pathogenesis of deep vein thrombosis in the surgical patients, the predisposing risk factors, and the available prophylactic modalities are discussed in this article. Recommendations for the use of various approaches in different risk categories are provided.

Irradiation-induced atherosclerosis: a factor in therapeutic planning.

Early primary head and neck cancers (stages I and II) and occult metastatic neck disease have caused debate regarding the choice between surgery and irradiation. The arguments for each are reviewed with a new consideration: the acceleration and/or induction of carotid atherosclerosis in irradiated patients. We present clinical case reports (n = 9), a retrospective clinical evaluation for the occurrence of carotid atherosclerosis in irradiated head and neck cancer patients (n = 57) and a comparison study of the extent and distribution of atherosclerosis in irradiated (n = 29) and nonirradiated head and neck cancer patients controlled for age, blood pressure, and tobacco use. The results show that carotid atherosclerosis is found in a wider anatomic distribution and to a greater extent in irradiated than in nonirradiated patients. We conclude that carotid atherosclerosis is induced and/or accelerated by neck irradiation. The implications as they relate to choice of treatment, to pretreatment evaluations, and to long-term follow-up are discussed.

Achieving compliance with influenza immunization of medical house staff and students. A randomized controlled trial.

OBJECTIVE: To determine the optimal method to increase influenza immunization rates of medical house staff and students. DESIGN: Prospective randomized trial and cross-sectional survey. STUDY GROUP: Four hundred forty-two internal medicine, obstetrics-gynecology, and general surgery residents and junior medical students. MEASUREMENTS: The four interventions employed were (1) an educational memorandum outlining vaccine indications sent to all study group members, (2) a personal letter mailed to a random sample of half of the remaining unimmunized persons, (3) a telephone call to half of the unimmunized letter recipients, and (4) vaccine offered directly to the remaining unimmunized persons in clinics and conferences. In addition, a questionnaire was administered to all persons requesting or offered vaccine. MAIN RESULTS: During the 3 weeks after the memorandum, 87 (20%) of 442 persons were immunized. Five weeks after the letter, 61 (34%) of persons receiving a letter and 30 (17%) of the no-letter controls (P = .0005) had been immunized. After the telephone call, there was a statistically insignificant trend toward increased compliance. In clinics and conferences, 90% of persons reached were immunized and 10% refused, largely extinguishing the effect of prior interventions. At completion of the study, 275 (62%) of 442 participants were immunized, 29 (7%) refused, and 138 (31%) were not reached. Questionnaire results revealed that only 32% had ever been previously immunized against influenza, yet 70% stated that they had worked despite having influenzalike symptoms. CONCLUSION: A high rate of immunization of house staff and medical students can be achieved most effectively by offering vaccine in clinics and conferences. Continued education about influenza immunization is necessary for physicians and medical students.