Evaluation of the Pulmonary Toxicity of Ambient Particulate Matter From Camp Victory, Iraq.

Anecdotal reports in the press and epidemiological studies suggest that deployment to Iraq and Afghanistan may be associated with respiratory diseases and symptoms in U.S. military personnel and veterans. Exposures during military operations were complex, but virtually all service members were exposed to high levels of respirable, geogenic dust. Inhalation of other dusts has been shown to be associated with adverse health effects, but the pulmonary toxicity of ambient dust from Iraq has not been previously studied. The relative toxicity of Camp Victory dust was evaluated by comparing it to particulate matter from northern Kuwait, a standard U.S. urban dust, and crystalline silica using a single intratracheal instillation in rats. Lung histology, protein levels, and cell counts were evaluated in the bronchoalveolar lavage fluid 1-150 d later. The Iraq dust provoked an early significant, acute inflammatory response. However, the level of inflammation in response to the Iraq dust, U.S. urban dust, and Kuwait dust rapidly declined and was nearly at control levels by the end of the study At later times, animals exposed to the Iraq, U.S. urban, or Kuwait dusts showed increased small airway remodeling and emphysema compared to silica-exposed and control animals without evidence of fibrosis or premalignant changes. The severity and persistence of pulmonary toxicity of these three dusts from the Middle East resemble those of a U.S. urban dust and are less than those of silica. Therefore, Iraq dust exposure is not highly toxic, but similar to other poorly soluble low-toxicity dusts.

A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium.

We present a differential equation model of the innate immune response to SARS-CoV-2 within the alveolar epithelium. Critical determinants of the viral dynamics and host response, including type I and type II alveolar epithelial cells, interferons, chemokines, toxins and innate immune cells, are included. We estimate model parameters, compute the within-host basic reproductive number, and study the impacts of therapies, prophylactics, and host/pathogen variability on the course of the infection. Model simulations indicate that the innate immune response suppresses the infection and enables the alveolar epithelium to partially recover. While very robust antiviral therapy controls the infection and enables the epithelium to heal, moderate therapy is of limited benefit. Meanwhile interferon therapy is predicted to reduce viral load but exacerbate tissue damage. The deleterious effects of interferon therapy are especially apparent late in the infection. Individual variation in ACE2 expression, epithelial cell interferon production, and SARS-CoV-2 spike protein binding affinity are predicted to significantly impact prognosis.

A new method for carbon isotopic analysis of protein.

The reaction of ninhydrin with amino acids can be used in carbon isotopic studies of protein. The reaction can be applied to extract as carbon dioxide only peptide-bonded carbon in proteinaceous material, thus avoiding most, if not all, contaminants. Test radiocarbon dates on ancient bone indicate that the method provides reliable ages, and stable carbon isotopic data suggest that our understanding of isotopic dietary reconstruction needs detailed examination. The technique should also be useful in biochemical tracing experiments and in global carbon budget studies, and the underlying principle may be applicable to other isotopes and molecules.

Carbon-14: direct detection at natural concentrations.

The (14)C atoms naturally present in a piece of 19th-century wood have been detected directly by means of a tandem Van de Graaff accelerator used as a high-energy mass spectrometer. The (14)C ions were easily resolved from interfering ions with the use of a DeltaE-E detector telescope (this telescope consists of a pair of detectors; one of them measures the specific ionization, DeltaE, and the sum of the signals from both detectors gives the total energy for each ion, ET). The technique offers a number of practical advantages.

Stable-carbon isotope ratios as a measure of marine versus terrestrial protein in ancient diets.

The stable-carbon isotope ratios for the flesh of marine and terrestrial animals from Canada's Pacific coast differ by 7.9 +/- 0.4 per mil, reflecting the approximately 7 per mil difference between oceanic and atmospheric carbon. This difference is passed on to human consumers. The carbon isotopic values (delta(13)C) for human collagen thus yield direct information on the relative amounts of marine and terrestrial foods in prehistoric diets.

Regulation of jun-B messenger RNA and AP-1 activity by light and a circadian clock.

The suprachiasmatic nuclei (SCN) of the hypothalamus comprise the primary pacemaker responsible for generation of circadian rhythms in mammals. Light stimuli that synchronize this circadian clock induce expression of the c-fos gene in rodent SCN, which suggests a possible role for Fos in circadian entrainment. Appropriate light stimuli also induce the expression of jun-B messenger RNA in the SCN of golden hamsters but only slightly elevate c-jun messenger RNA levels. In addition, light increases the amount of a protein complex in the SCN that binds specifically to sites on DNA known to mediate regulation by the AP-1 transcription factor. The photic regulation of both jun-B messenger RNA expression and AP-1 binding activity is dependent on circadian phase: only light stimuli that shift behavioral rhythms induce jun-B and AP-1 expression. Thus, light and the circadian pacemaker interact to regulate a specific set of immediate-early genes in the SCN that may participate in entrainment of the circadian clock.

New dates on northern yukon artifacts: holocene not upper pleistocene.

New radiocarbon dates on four artifacts that were thought to provide evidence for human occupation of the Yukon Territory during the upper Pleistocene indicate that all four are of late Holocene age. The original radiocarbon age obtained for one artifact (the so-called "Old Crow flesher") was in error by almost 26,000 years.

Photic and circadian regulation of c-fos gene expression in the hamster suprachiasmatic nucleus.

Photic information entrains a circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus to environmental light/dark cycles. To determine whether light regulates c-fos gene expression in the SCN, we have measured c-fos mRNA levels in the SCN of the golden hamster. We report that, during the subjective night, light causes a rapid increase in levels of c-fos mRNA in the SCN. Light pulses of 5 min duration are sufficient to induce c-fos mRNA, and the highest mRNA levels occur 30 min following the onset of light. The minimum level of illumination required to induce an increase in c-fos mRNA is indistinguishable from the minimum irradiance that produces a phase shift in the hamster's circadian rhythm of activity. In addition, the induction of c-fos mRNA in the SCN by light is itself under circadian regulation. Light induction of c-fos mRNA occurs only during the subjective night, at circadian times when photic phase shifting of activity occurs. Taken together, these data suggest that c-fos may be a molecular component of the photic pathway for entrainment of mammalian circadian rhythms.

Pain and its relationship with muscle strength and proprioception in knee OA: results of an 8-week home exercise pilot study.

Muscle strength and proprioception deficits have been recognized in knee OA. Pain is the symptomatic hallmark of knee OA. Indirect evidence suggests that muscle strength and proprioception deficits may be interrelated and that pain may have a confounding influence on the measurement of these factors in knee OA. However, these relationships have never been clearly evaluated. Therefore, the purpose of this investigation was to investigate relationships between pain, muscle strength, and proprioception in subjects with knee OA before and after an 8-week home exercise program. This study evaluated thirty-eight subjects with knee OA. Subjects were taught standard quadriceps strengthening exercises that were to be performed daily at home. Pain, muscle strength, and proprioceptive function were measured at baseline and after 8 weeks of therapy. Significant improvements in pain (42%, p<0.001) and quadriceps muscle strength (30%, p<0.001) were noted. Significant indirect associations were observed between pain and both muscle strength (rho=-0.39, p=0.01) and proprioceptive acuity (rho=-0.35, p=0.03) at baseline. Changes in pain were directly associated with changes in muscle strength (rho=0.45, p=0.005) and proprioceptive acuity (rho=0.41, p=0.01) with exercise. The association of pain with both muscle strength and proprioception should prompt future studies to consider and adjust for the influence of pain on neuromuscular factors in knee OA.

Regulation of the Osmotin Gene Promoter.

By introducing a chimeric gene fusion of the osmotin promoter and [beta]-glucuronidase into tobacco by Agrobacterium-mediated transformation, we have demonstrated a very specific pattern of temporal and spatial regulation of the osmotin promoter during normal plant development and after adaptation to NaCl. We have found that the osmotin promoter has a very high natural level of activity in mature pollen grains during anther dehiscence and in pericarp tissue at the final, desiccating stages of fruit development. GUS activity was rapidly lost after pollen germination. The osmotin promoter thus appears to be unique among active pollen promoters described to date in that it is active only in dehydrated pollen. The osmotin promoter was also active in corolla tissue at the onset of senescence. Adaptation of plants to NaCl highly stimulated osmotin promoter activity in epidermal and cortex parenchyma cells in the root elongation zone; in epidermis and xylem parenchyma cells in stem internodes; and in epidermis, mesophyll, and xylem parenchyma cells in developed leaves. The spatial and temporal expression pattern of the osmotin gene appears consistent with both osmotic and pathogen defense functions of the gene.

Trends in cigarette smoking and physicians' advice to quit smoking among people with diabetes in the U.S.

OBJECTIVE: This study describes changes in the distribution of cigarette smoking and in physicians' advice to quit smoking among the U.S. population with and without diabetes from the mid-1970s to 1990. RESEARCH DESIGN AND METHODS: Data on self-reported smoking status, physicians' advice to quit smoking, history of diabetes, and demographic characteristics were obtained from the 1974, 1985, and 1990 National Health Interview Surveys. We examined the age-adjusted prevalence of smoking and physicians' advice to quit smoking by race, sex, and educational level among individuals with diabetes and those without diabetes. RESULTS: The prevalence of smoking decreased 9.8 percentage points from 1974 to 1990 among individuals with diabetes (from 35.6 to 25.8%, P < 0.01) and 11.7 percentage points among those without diabetes (from 37.3 to 25.6%, P < 0.01). For all years, younger individuals, men, and people with less than a high school education were more likely to smoke, regardless of diabetes status. Among individuals who had ever smoked, those with diabetes were more likely to have received advice to quit than those without diabetes; from 1974 to 1990, the percentage advised to quit smoking by a physician increased from 35.1 to 58.4% for smokers with diabetes and from 26.8 to 46.0% for smokers without diabetes. CONCLUSIONS: Despite decreases in smoking prevalence over time, people with diabetes are still as likely to smoke as those without diabetes. More than 40% of smokers with diabetes currently report never having received advice from a physician to quit smoking. Health care providers should increase their efforts to reduce smoking among people with diabetes.

Diabetes trends in the U.S.: 1990-1998.

OBJECTIVE: To examine trends in diabetes prevalence in the U.S. RESEARCH DESIGN AND METHODS: This study was conducted via telephone surveys in states that participated in the Behavioral Risk Factor Surveillance System between 1990 and 1998. The participants consisted of noninstitutionalized adults aged 18 years or older. The main outcome measure was self-reported diabetes. RESULTS: The prevalence of diabetes rose from 4.9% in 1990 to 6.5% in 1998--an increase of 33%. Increases were observed in both sexes, all ages, all ethnic groups, all education levels, and nearly all states. Changes in prevalence varied by state. The prevalence of diabetes was highly correlated with the prevalence of obesity (r = 0.64, P<0.001). CONCLUSIONS: The prevalence of diabetes continues to increase rapidly in the U.S. Because the prevalence of obesity is also rising, diabetes will become even more common. Major efforts are needed to alter these trends.

Light pulses suppress responsiveness within the mouse photic entrainment pathway.

We have characterized a decrease in photic responsiveness of the mammalian circadian entrainment pathway caused by light stimulation. Phase delays of the running-wheel activity rhythm were used to quantify the photic responsiveness of the circadian system in mice (C57BL/6J). In an initial experiment, the authors measured the responsiveness to single "saturating" light pulses ("white" fluorescent light; approximately 1876 [microW; 15 min). In two additional experiments, the authors measured responses to this stimulus at several time points following a saturating pulse at CT 14 or CT 16. Data from these experiments were analyzed in two manners. Experiment 2 was analyzed assuming that the phase of the circadian pacemaker was unchanged by an initial pulse, and Experiment 3 was analyzed assuming that the initial pulse induced an instantaneous phase delay. Results reveal a significant reduction in responsivity to light that persists for at least 2 h and possibly up to 4 h after the initial stimulus. Immediately after the stimulus, the responsiveness of the photic entrainment pathway was reduced to levels < or = 12% of normal. After 2 h, the responsiveness was < or = 42% of normal, and by 4 h, responsiveness had recovered to levels that were < or = 60% of normal (levels not statistically different from controls). By the following circadian cycle, responsiveness was more completely recovered, although the magnitude of some phase delays remained < or = 85% of normal. These major reductions in the magnitude of phase delays (and phase response curve amplitude) caused by saturating light pulses confound interpretations of two-pulse experiments designed to measure the rate of circadian phase delays. In addition, the time course for this reduced responsiveness may reflect the time course of cellular and molecular events that underlie light-induced resetting of the mammalian circadian pacemaker.

Photoperiodic time measurement in tau mutant hamsters.

Photoperiodic regulation of testicular function was investigated in homozygous tau mutant hamsters; these animals have an innate circadian period of about 20 h. In 20-h light:dark (LD) cycles, the minimum photoperiod required to prevent testicular regression was between 10.0 and 11.5 h per 20-h cycle (equivalent to 12.0-13.8 circadian hours). This was proportionally similar to the minimum photoperiod necessary to prevent regression in wild-type hamsters maintained in 24-h LD cycles. To examine the shape of the photoperiodic photosensitivity curve in homozygous tau mutant hamsters, the authors measured the effects of different T cycles on testicular maintenance. Entrainment to LD 1:18.0 and LD 1:20.5 partially or completely prevented gonadal regression in homozygous tau mutant hamsters, but LD 1:19.4 did not prevent regression. When considered in terms of circadian time, the photoperiodic photosensitivity curve for homozygous tau mutant hamsters was similar to that described previously for wild-type hamsters. The results indicate that, as in wild-type hamsters, photoperiodic regulation of reproduction is regulated by circadian photosensitivity in homozygous tau mutant hamsters. Because tau mutant hamsters measure day length against a time base of 20 h, the circadian pacemaker that measures day length might be the same as that which generates circadian rhythmicity in locomotor activity. The authors' data leave open the question of whether the tau mutation has had effects on the control of reproduction that are not directly attributable to its effects on the period of the circadian oscillator.

Immunocytochemical localization of serotonergic fibers innervating the ocular circadian system of Aplysia.

The isolated eye of the mollusc, Aplysia californica, contains a circadian pacemaker whose phase can be regulated by serotonin. The results of previous biochemical and physiological studies indicate that serotonin is used as a transmitter of circadian information in the eye. Although the effects of serotonin on various physiological processes in the Aplysia eye have been studied, very little is known about the anatomy of the serotonergic innervation. We have examined the innervation of the eye using immunocytochemical methods. Serotonin-immunoreactive processes were observed in the optic nerve, in the accessory optic nerves, in the connective tissue capsule surrounding the eye, and within the eye itself. There appeared to be two sources of serotonergic input to the eye of Aplysia. One set of immunoreactive fibers was contained in the optic nerve and entered the eye in the neuropil region before radiating outward towards the peripheral retina in the layer below the photoreceptor cell bodies. A second serotonin-immunoreactive input to the eye entered from the accessory optic nerves and these fibers formed a dense plexus of fibers in the connective tissue capsule surrounding the eye. Serotonin-immunoreactive fibers from the plexus penetrated the eye and appeared to terminate in the peripheral portion of the retina. No serotonin-immunoreactive cell bodies were observed in the eye, nerves, or connective tissue capsule. These results support the hypothesis that serotonergic fibers innervate the retina of Aplysia and that these fibers travel through two distinct anatomical pathways: the optic nerve and the accessory optic nerves.

Smoking policies of licensed child day-care centers in the United States.

The authors analyzed data from a national survey of 2003 directors of licensed child day-care centers to determine employee smoking policies, measure compliance with state and local employee smoking regulations for child day-care centers and state clean indoor air laws, and to estimate the extent of exposure to environmental tobacco smoke in these settings. Forty states regulated employee smoking in child day-care centers, but only three states required day-care centers to be smoke-free indoors. More than 99% of licensed child day-care centers had employee smoking policies that complied with the appropriate state or local smoking regulations. Nearly 55% of centers were smoke-free indoors and outdoors, and 26% were smoke-free indoors only. The best predictors of more stringent employee smoking policies were location in the West or South, smaller size, independent ownership, or having written smoking policies. Despite the presence of strong smoking policies at the majority of licensed child day-care centers, more than 752,000 children in the United States are at risk for environmental tobacco smoke exposure in these settings. Health care professionals and parents should insist that child day-care centers be smoke-free indoors and, preferably, smoke-free indoors and outdoors.

Alcohol as a risk factor for fall injury events among elderly persons living in the community.

OBJECTIVE: To determine if alcohol use is a risk factor for fall injury events among community-dwelling older persons. DESIGN: Case-control study. SETTING: South Miami Beach, Florida. PARTICIPANTS: 320 persons 65 or older who sought treatment at six area hospitals for injuries resulting from falls; 609 controls, matched for sex and age, selected randomly from Health Care Financing Administration (Medicare) files. MAIN INDEPENDENT VARIABLES: Self-reported current alcohol use. RESULTS: No association was found between fall injury events and average weekly alcohol use. CONCLUSIONS: Further efforts at reducing injuries to older persons from falls should concentrate on other modifiable risk factors, including adequate treatment of underlying medical conditions, reducing inappropriate psychotropic medication use, and installing safety devices in the home.

Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins.

OBJECTIVE: To better define the role of multiple risk factors for cytotoxic Clostridium difficile-associated diarrhea. DESIGN: Case-control study. SETTING: A Veterans Affairs Medical Center. PATIENTS: Thirty-three case patients with C difficile-associated diarrhea. Two control groups were used: one group consisted of 32 patients from the same ward as the case patients, and one group consisted of 34 patients with nosocomial diarrhea and negative C difficile toxin assays. INTERVENTION: None. RESULTS: Multivariate analyses revealed that exposure to second- or third-generation cephalosporins was the most important independent risk factor, even after controlling for other antimicrobial use (odds ratio [OR] = 8.3, 95% confidence interval [CI95] = 1.4 to 48.9 compared to ward controls; OR = 9.6, CI95 = 2.1 to 44.1 compared with diarrhea controls). Persons exposed to two or more antimicrobials simultaneously were at substantially elevated risk (OR = 18.7, CI95 = 4.1 to 85.8 compared with ward controls; OR = 21.5, CI95 = 3.2 to 141.9 compared with diarrhea controls). CONCLUSION: Physicians should consider carefully the appropriateness of second- and third-generation cephalosporin use and combination antimicrobial therapy, especially during nosocomial C difficile-associated diarrhea outbreaks (Infect Control Hosp Epidemiol 1994;15:88-94).

Physical abuse among high school students. Prevalence and correlation with other health behaviors.

OBJECTIVE: To better understand the epidemiology of physical abuse among adolescents. DESIGN: School-based survey of students in grades 9 through 12. SETTING: Twenty-five schools throughout Oregon in 1993. MAIN OUTCOME MEASURES: Prevalence of ever being physically abused, prevalence of most recent occurrence of physical abuse, and correlation of physical abuse with high-risk health behaviors. RESULTS: Of the 1957 respondents, 31.5% reported having ever been physically abused, with female subjects (34.6%) more likely than male subjects (28.0%) to have ever been abused. Overall, 3.7% of students had been physically abused in the past week, 7.8% in the past month, and 16.3% in the past year. Based on multivariate models, students physically abused in the past year were more likely than students who had never been physically abused to engage in a variety of high-risk behaviors; these included weapon carrying (odds ratio, 1.9), suicidal ideation (odds ratio, 2.1), cigarette smoking (odds ratio, 1.8), cocaine use (odds ratio, 3.2), or multiple sexual partners (odds ratio, 1.9). CONCLUSIONS: Physical abuse, an important problem among high school students, is correlated with many high-risk behaviors. Using consistent definitions, periodic surveys of children about physical abuse and other types of violent behavior are needed to provide better estimates of the extent of these problems.

Comparison of visual sensitivity for suppression of pineal melatonin and circadian phase-shifting in the golden hamster.

Visual sensitivity for light suppression of pineal melatonin was measured in golden hamsters using 300 s stimuli of monochromatic light (503 nm) in constant darkness. Increasing stimulus irradiance caused a monotonic decrease in pineal-melatonin content. Irradiance greater than 3.5 X 10(10) photons cm-2.s-1 caused significant reductions of melatonin in the hamster pineal. Saturation of the response occurred above 10(11) photons cm-2.s-1 and melatonin levels were suppressed to approximately 7% of levels measured in unstimulated animals. Using a 4-parameter Naka-Rushton function to fit the data, the half-saturation constant for suppression of pineal melatonin was 1.3 x 10(10) photons cm-2.s-1. The sensitivity of the photic-entrainment pathway for circadian rhythms has also been measured in the hamster using identical stimulus parameters. Light suppression of pineal melatonin was 25 times (1.4 log units) more sensitive to irradiance than the phase-shifting response measured for the circadian rhythm of running-wheel activity (comparing the half-saturation constants for the two responses). Both of these responses, however, are much less sensitive to light than other visual responses measured behaviorally in the golden hamster.