Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.

BACKGROUND: Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS: Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. RESULTS: Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. CONCLUSIONS: Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

Particulate reactive oxygen species on total suspended particles - measurements in residences in Austin, Texas.

The biologically relevant characteristics of particulate matter (PM) in homes are important to assessing human health. The concentration of particulate reactive oxygen species (ROS) was assessed in eight homes and was found to be lower inside (mean ± s.e. = 1.59 ± 0.33 nmol/m3 ) than outside (2.35 ± 0.57 nmol/m3 ). Indoor particulate ROS concentrations were substantial and a major fraction of indoor particulate ROS existed on PM2.5 (58 ± 10%), which is important from a health perspective as PM2.5 can carry ROS deep into the lungs. No obvious relationships were evident between selected building characteristics and indoor particulate ROS concentrations, but this observation would need to be verified by larger, controlled studies. Controlled experiments conducted at a test house suggest that indoor ozone and terpene concentrations substantially influence indoor particulate ROS concentrations when outdoor ozone concentrations are low, but have a weaker influence on indoor particulate ROS concentrations when outdoor ozone concentrations are high. The combination of substantial indoor concentrations and the time spent indoors suggest that further work is warranted to assess the key parameters that drive indoor particulate ROS concentrations.

Characterizing the bacterial communities in retail stores in the United States.

The microorganisms present in retail environments have not been studied in detail despite the fact that these environments represent a potentially important location for exposure. In this study, HVAC filter dust samples in 13 US retail stores were collected and analyzed via pyrosequencing to characterize the indoor bacterial communities and to explore potential relationships between these communities and building and environmental parameters. Although retail stores contained a diverse bacterial community of 788 unique genera, over half of the nearly 118K sequences were attributed to the Proteobacteria phylum. Streptophyta, Bacillus, Corynebacterium, Pseudomonas, and Acinetobacter were the most prevalent genera detected. The recovered indoor airborne microbial community was statistically associated with both human oral and skin microbiota, indicating occupants are important contributors, despite a relatively low occupant density per unit volume in retail stores. Bacteria generally associated with outdoor environments were present in the indoor communities with no obvious association with air exchange rate, even when considering relative abundance. No significant association was observed between the indoor bacterial community recovered and store location, store type, or season. However, predictive functional gene profiling showed significant associations between the indoor community and season. The microbiome recovered from multiple samples collected months apart from the same building varied significantly indicating that caution is warranted when trying to characterize the bacterial community with a single sampling event.

Optically pumped microplasma rare gas laser.

The optically pumped rare-gas metastable laser is a chemically inert analogue to three-state optically pumped alkali laser systems. The concept requires efficient generation of electronically excited metastable atoms in a continuous-wave (CW) electric discharge in flowing gas mixtures near atmospheric pressure. We have observed CW optical gain and laser oscillation at 912.3 nm using a linear micro-discharge array to generate metastable Ar(4s, 1s(5)) atoms at atmospheric pressure. We observed the optical excitation of the 1s(5) → 2p(9) transition at 811.5 nm and the corresponding fluorescence, optical gain and laser oscillation on the 2p(10) ↔ 1s(5) transition at 912.3 nm, following 2p(9)→2p(10) collisional energy transfer. A steady-state kinetics model indicates efficient collisional coupling within the Ar(4s) manifold.

Aerosol-phase activity of iodine captured from a triiodide resin filter on fine particles containing an infectious virus.

AIMS: To avoid interference by water-iodine disinfection chemistry and measure directly the effect of iodine, captured from a triiodide complex bound to a filter medium, on viability of penetrating viral particles. METHODS AND RESULTS: Aerosols of MS2 coli phage were passed through control P100 or iodinated High-Efficiency Particulate Air media, collected in plastic bags, incubated for 0-10 min, collected in an impinger containing thiosulphate to consume all unreacted iodine, plated and enumerated. Comparison of viable counts demonstrated antimicrobial activity with an apparent half-life for devitalization in tens of seconds; rate of kill decreased at low humidity and free iodine was captured by the bags. CONCLUSIONS: The results support the mechanism of near-contact capture earlier proposed; however, the disinfection chemistry in the aerosol phase is very slow on the time scale of inhalation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that disinfection by filter-bound iodine in the aerosol phase is too slow to be clinically significant in individual respiratory protection, but that it might be of benefit to limit airborne transmission of infections in enclosed areas.

Standard method for deposition of dry, aerosolized, silica-coated Bacillus spores onto inanimate surfaces.

AIMS: To evaluate a standard aerosolization method for uniformly depositing threat-representative spores onto surfaces. METHODS AND RESULTS: Lyophilized Bacillus anthracis ΔSterne spores, coated in silica, were aerosolized into a containment chamber and deposited onto nine surface types by two independent laboratories. Laboratory A produced a mean loading concentration of 1·78 × 10(5) CFU cm(-2) ; coefficient of variation (CV) was <40% for 96% of samples. Laboratory B produced a mean loading concentration of 7·82 × 10(6) CFU cm(-2) ; 68% of samples demonstrated CV <40%. CONCLUSIONS: This method has been shown to meet the goal of loading threat-representative spores onto surfaces with low variability at concentrations relevant to the Department of Defense. SIGNIFICANCE AND IMPACT OF THE STUDY: As demonstrated in 2001, a biological attack using anthrax disseminated as a dry powder is a credible threat. This method will provide a means to load spores onto surfaces that mimic a 'real-world' scenario of an aerosolized anthrax attack. The method has utility for evaluating sporicidal technologies and for nondecontamination studies, for example fate and transport or reaerosolization.

Quantification of genes and gene transcripts for microbial perchlorate reduction in fixed-bed bioreactors.

AIMS: Optimization of full-scale, biological perchlorate treatment processes for drinking water would benefit from knowledge of the location and quantity of perchlorate-reducing bacteria (PRB) and expression of perchlorate-related genes in bioreactors. The aim of this study was to quantify perchlorate removal and perchlorate-related genes (pcrA and cld) and their transcripts in bioreactors and to determine whether these genes or transcripts could serve as useful biomarkers for perchlorate treatment processes. METHODS AND RESULTS: Quantitative PCR (qPCR) assays targeting pcrA and cld were applied to two pilot-scale, fixed-bed bioreactors treating perchlorate-contaminated groundwater. pcrA and cld genes per microgram of DNA were two- to threefold higher and three- to fourfold higher, respectively, in the bioreactor showing superior perchlorate-removal performance. In a laboratory-scale bioreactor, quantities of pcrA and cld genes and transcripts were compared under two distinct performance conditions (c.60 and 20% perchlorate removal) for a 5-min empty bed contact time. cld genes per microgram of DNA were approximately threefold higher and cld transcripts per microgram of RNA were approximately sixfold higher under the higher perchlorate-removal condition. No differences in pcrA genes or transcripts per microgram of DNA or RNA, respectively, were detected between the c.60 and 20% perchlorate-removal conditions, possibly because these assays did not accurately quantify pcrA genes and transcripts in the mixed culture present. CONCLUSIONS: Quantities of cld genes and transcripts per microgram of DNA and RNA, respectively, were found to be higher when perchlorate removal was higher. However, quantities of pcrA and cld genes or transcripts were not found to directly correlate with perchlorate-removal rates. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this study represents the first application of qPCR assays to quantify perchlorate-related genes and transcripts in continuous-flow bioreactors. The results indicate that cld gene and transcript quantities can provide insights regarding the quantity, location and gene expression of PRB in bioreactors.

Space-time analysis of COVID-19 cases and SARS-CoV-2 wastewater loading: A geodemographic perspective.

Severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) continues to effect communities across the world. One way to combat these effects is to enhance our collective ability to remotely monitor community spread. Monitoring SARS-CoV-2 in wastewater is one approach that enables researchers to estimate the total number of infected people in a region; however, estimates are often made at the sewershed level which may mask the geographic nuance required for targeted interdiction efforts. In this work, we utilize an apportioning method to compare the spatial and temporal trends of daily case count with the temporal pattern of viral load in the wastewater at smaller units of analysis within Austin, TX. We find different lag-times between wastewater loading and case reports. Daily case reports for some locations follow the temporal trend of viral load more closely than others. These findings are then compared to socio-demographic characteristics across the study area.

Analysis of residual chemicals on filtering facepiece respirators after decontamination.

The N95 filtering facepiece respirator (FFR) is commonly used to protect individuals from infectious aerosols. Health care experts predict a shortage of N95 FFRs if a severe pandemic occurs, and an option that has been suggested for mitigating such an FFR shortage is to decontaminate and reuse the devices. Before the effectiveness of this strategy can be established, many parameters affecting respiratory protection must be measured: biocidal efficacy of the decontamination treatment, filtration performance, pressure drop, fit, and toxicity to the end user post treatment. This research effort measured the amount of residual chemicals created or deposited on six models of FFRs following treatment by each of 7 simple decontamination technologies. Measured amounts of decontaminants retained by the FFRs treated with chemical disinfectants were small enough that exposure to wearers will be below the permissible exposure limit (PEL). Toxic by-products were also evaluated, and two suspected toxins were detected after ethylene oxide treatment of FFR rubber straps. The results provide encouragement to efforts promoting the evolution of effective strategies for decontamination and reuse of FFRs.

Cs 894.3 nm laser pumped by photoassociation of Cs-Kr pairs: excitation of the Cs D(2) blue and red satellites.

Lasing on the D(1) transition (6P1/22-->6S1/22) of Cs has been observed by photoassociating Cs-Kr atomic pairs with a tunable, pulsed dye laser. Pumping of the blue or red satellites of the Cs D(2) line (62P3/2<==>62S1/2), peaking at approximately 841.1 nm and approximately 853 nm (respectively) in Cs/Kr/C(2)H(6) gas mixtures, provides a photodissociation laser in which the CsKr excimer parent molecule is not, at any point in the pumping process, in a bound electronic state. Relative to the absorbed pump pulse energy, laser slope efficiencies greater than or approximately 5% have been measured when the Cs number density is in the range of 5x10(14)-1.5x10(15) cm(-3) and the pump wavelength is 841.1 nm. Direct photoexcitation of the Cs 6P3/22 state at 852.1 nm under these conditions is a less efficient pathway for pumping the 894.3 nm laser, presumably as a result of competing nonlinear optical processes such as 1+2 resonantly enhanced multiphoton ionization of the alkali atom.

Droplet distribution and airborne bacteria in an experimental shower unit.

Although human exposure to water aerosols is common in residential showers, the droplet distribution patterns generated in showers are not well understood nor is the bacteria released during shower operation. In this study, a two-phase flow Particle Tracking Velocimetry (PTV) algorithm was successfully used to characterize the spatial spray pattern and velocity field in two experimental showers (one low-flow and one high-flow). In addition, the airborne bacteria present in the shower over nearly 5 months of controlled operation was determined for both showers. The results indicate that the droplet velocity out of the low-flow showerhead (which had fewer orifices) was significantly higher than that out of the high-flow showerhead resulting in a higher aerosol number concentration in the low-flow shower and more consistent wetting of the shower wall. Both showerheads generated droplets in the respirable range and genera of potential health concern were observed in the shower aerosols measured both prior to and following shower operation. The study provides one of the first visualizations of droplet spray patterns in residential showers and provides insight into the airborne bacteria present in showers.

The Microbiome of the Built Environment and Human Behavior: Implications for Emotional Health and Well-Being in Postmodern Western Societies.

It is increasingly evident that inflammation is an important determinant of cognitive function and emotional behaviors that are dysregulated in stress-related psychiatric disorders, such as anxiety and affective disorders. Inflammatory responses to physical or psychological stressors are dependent on immunoregulation, which is indicated by a balanced expansion of effector T-cell populations and regulatory T cells. This balance is in part driven by microbial signals. The hygiene or "old friends" hypothesis posits that exposure to immunoregulation-inducing microorganisms is reduced in modern urban societies, leading to an epidemic of inflammatory disease and increased vulnerability to stress-related psychiatric disorders. With the global trend toward urbanization, humans are progressively spending more time in built environments, thereby, experiencing limited exposures to these immunoregulatory "old friends." Here, we evaluate the implications of the global trend toward urbanization, and how this transition may affect human microbial exposures and human behavior.

Efficacy and safety of orally/sublingually, intranasally, and intraperitoneally administered recombinant murine interferon in the treatment of murine encephalomyocarditis virus.

Interferons (IFN) have been shown to be effective in protecting animals against lethal viral infections when administered systemically in relatively high doses. Intraperitoneal (i.p.) injection of mice with encephalomyocarditis virus (EMCV) gives rise to a rapidly progressive fatal disease characterized by central nervous system involvement and encephalitis. IFN-alpha has been shown to be effective in protecting mice against lethal EMCV infection when given via parenteral and oral/sublingual routes. The current study was designed to explore the ability of orally/sublingually and intranasally (i.n.) administered IFN-alpha to treat mice infected with EMCV in support of a planned clinical trial to evaluate efficacy of oral IFN-alpha in human viral infections. The primary objective of the study was to determine the efficacy of recombinant murine IFN-alpha (rMuIFN-alpha) in the treatment of mice infected with 100 LD(50) EMCV following oral, i.n., and i.p. administration at doses of 20,000 and 100,000 IU. The results of the current experiment did not indicate protection from infection with EMCV in mice that received IFN by the i.n. or oral/sublingual routes. The negative controls, infection of mice with 100 LD(50) of EMCV followed by treatment with excipient via all three routes, resulted in death of nearly all mice, as expected. The positive control, treatment of EMCV-infected (100 LD(50)) mice with rMuIFN-alpha via the i.p. route, was successful in protecting a significant number of mice from death compared with matched controls. This study points out the need to determine the optimum conditions for administration of oral/sublingual or i.n. IFN to insure maximum efficacy against viral infections.

Noradrenergic and peptidergic innervation of the amphibian spleen: comparative studies.

Spleens from representatives of the three amphibian orders were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence to detect catecholamines and immunocytochemistry to detect several neural antigens. Nerve fibers are scattered throughout the spleens of adult salamanders (Taricha torosa, Notophthalmus viridescens, and Ambystoma mexicanum). A less abundant but similarly diffuse pattern of innervation characterizes the spleen of the caecilian, Typhlonectes sp. The spleen of the adult frog, Xenopus laevis, is separated into clearly defined compartments of red pulp and white pulp, much as is seen in the mammalian spleen. As in mammals, sympathetic innervation of the Xenopus spleen is noradrenergic (NA) and confined to the white pulp. The white pulp of Xenopus spleen also contains fibers which stain for neuropeptide Y and substance P. The spleen of the anuran, Rana pipiens, is also highly compartmentalized, with tyrosine hydroxylase positive fibers in proximity to blood vessels. These findings provide an anatomical substrate for neural-immune interactions in the Amphibia.

Sympathetic innervation of the amphibian spleen: developmental studies in Xenopus laevis.

Spleens from larval and adult South African clawed frogs (Xenopus laevis) were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence for norepinephrine. Innervation of the larval Xenopus spleen is barely detectable at stage 54 and gradually increases during prometamorphosis (stage 57/58) until metamorphic climax (stage 66). This development of innervation late in the larval life of the animal was highly sensitive to environmental conditions and to rapidity at which development occurred. Prevention of overt metamorphosis by sodium perchlorate blockade prevented the development of noradrenergic (NA) splenic innervation in some, but not all, tadpoles examined. Depletion of T-lymphocytes by early larval thymectomy did not alter the kinetics or pattern of splenic NA innervation.

Repeatability and validity of astigmatism measurements.

BACKGROUND: As more patients inquire about refractive surgical procedures, the measurement of astigmatism prior to surgery becomes more important in assessing refractive outcome. Knowledge of the repeatability of the astigmatism measurement allows one to distinguish a true change in cylinder power from measurement error. METHODS: Forty adults with structurally normal eyes and refractive errors were evaluated for the repeatability of astigmatic refractive error measures. Noncycloplegic and cycloplegic measurements of refractive astigmatism were made by retinoscopy, subjective refraction, and autorefraction. All measures were made at 2 visits within 2 weeks by the same examiner. Difference versus mean plots and the 95% limits of agreement of each technique determined the repeatability of a measurement and the agreement between the methods of measurement. RESULTS: The most reliable measure of astigmatic refractive error was cycloplegic autorefraction, with 95% limits of agreement of +/- 0.28 D, followed by noncycloplegic autorefraction (+/- 0.35 D) and cycloplegic subjective refraction (+/- 0.44 D). Noncycloplegic retinoscopy was the least reliable astigmatic refractive error measure, with interoccasion 95% limits of agreement of +/- 1.02 D. The most repeatable measurement of cylinder axis was cycloplegic autorefraction; none of the measurements differed by 10 degrees or more. The least repeatable measurement was noncycloplegic retinoscopy; 40% of the measurements differed by 10 degrees or more. CONCLUSION: For studies seeking to measure changes in astigmatism in normal eyes, cycloplegic autorefraction is the method of choice.

Norepinephrine as a growth stimulating factor in bacteria--mechanistic studies.

Catecholamines (norepinephrine, epinephrine, dopamine) enhance the growth of several species of gram-negative bacteria. Since catechol rings are known siderophores in bacteria, the administration of catecholamines may enhance growth by improving iron uptake in growth-limiting media, serving as auxiliary siderophores. We have tested the iron content in bacterial growth media which are known to support rapid growth and "slow growth" media. Additionally, we have examined the uptake of 3H-norepinephrine, to determine whether the catecholamine is actually taken into the bacteria or is merely adsorbed to the outside of the bacteria. Finally, we have been examining the supernatants produced by culturing bacteria with norepinephrine. These supernatants have been shown to have the capacity to enhance growth of naive cultures of bacteria, and are suggested to contain an "autoinducer of growth". We have found that both fast-growth and slow-growth media contain similar concentrations of iron, and that these levels do not change in most supernatants from NE-supplemented bacterial cultures. Examination of culture supernatants from NE-supplemented bacteria under different temperature conditions reveals some interesting differences. First, culture supernatant from NE-treated Escherichia coli, cultured at 37 degrees C, when examined by HPLC, exhibits a change in the norepinephrine content over time which is not seen in supernatant from 21 degrees C cultures or other media treatments. Second, the 37 degrees C culture NE-supplemented E. coli supernatant was significantly more effective in enhancing growth of three bacterial species than any other culture method other than NE-supplementation itself (this includes supernatant from NE-supplemented cultures of the other two species as well as supernatants from unsupplemented cultures of all three species).

Immune alterations in three mouse strains following 2-deoxy-D-glucose administration.

Using 2-deoxy-D-glucose (2-DG)-induced stress, our laboratory has developed studies to define stress effects on immune responses. Here, we report effects of increasing doses of 2-DG on the immune response of BALB/c, C57BL/6 and BDF(1) mice 2 h after three injections of 0 to 2000 mg/kg of 2-DG. Female 4- to 5-week-old mice were euthanized and blood and spleens were collected. A suspension of partially purified mature T splenocytes was obtained by negative selection using J11.d2 antibodies. Glucose and corticosterone levels were measured in the plasma of each mouse. Splenocyte and mature T splenocyte suspensions were tested in in vitro proliferation assays with or without concanavalin A. Splenocytes were analyzed for the following cell-surface markers: CD3, TCR alpha/beta, CD4, CD8 and major histocompatibility complex (MHC) Class II. Significant increases in blood glucose levels were observed in C57BL/6 and BALB/c strains with the highest 2-DG dose (p<0.05). Corticosterone levels were higher in BDF(1) mice and C57BL/6 mice following the administration of 1000 and 2000 mg/kg of 2-DG, respectively (p<0.01). In vitro proliferation of mature T splenocytes in the presence of concanavalin A was decreased in BDF(1) (p<0.05) but not in BALB/c and C57BL/6 mice. In addition, in BDF(1) mice the decrease was highly correlated with an increase of CD3+ and TCR alpha/beta+ cells in the spleen. These results demonstrated high variability in the response of different mouse strains to 2-DG-induced stress.

A fungal vapor-phase bioreactor for the removal of nitric oxide from waste gas streams.

Ground-level O3 formation is becoming a major concern in many cities due to recent tightening of O3 regulations. To control O3 formation, more efficient treatment processes for O3 precursors, such as NOx and volatile organic compounds (VOCs), are needed. One promising new technology for removing both NOx and VOCs from off-gas streams is biofiltration, a simple process whereby contaminated air is passed through a biologically active packed bed. In this study, a toluene-degrading fungal bioreactor was used to treat an aerobic gas stream contaminated with NO. The fungal bioreactor removed 93% of the inlet 250-ppmv NO at an empty bed contact time (EBCT) of 1 min when supplied with 90 g/m3/hr toluene. The presence of NH4+ concentrations greater than 0.4 mg NH3/g dry packing medium, however, resulted in poor NO removal. The bioreactor achieved a maximum toluene elimination capacity of 270 g/m3/hr and maintained greater than 95% toluene removal efficiencies over the 175-day study period.

Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain.

The purpose of this double-blind, randomized, parallel, multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery. Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups. There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy. The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group.