Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome.

A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg-1). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.

Lanthanide-based laser-induced phosphorescence for spray diagnostics.

Laser-induced phosphorescence (LIP) is a relatively recent and versatile development for studying flow dynamics. This work investigates certain lanthanide-based molecular complexes for their use in LIP for high-speed sprays. Lanthanide complexes in solutions have been shown to possess long phosphorescence lifetimes (∼1-2 ms) and to emit light in the visible wavelength range. In particular, europium and terbium complexes are investigated using fluorescence/phosphorescence spectrometry, showing that europium-thenoyltrifluoracetone-trioctylphosphineoxide (Eu-TTA-TOPO) can be easily and efficiently excited using a standard frequency-tripled Nd:YAG laser. The emitted spectrum, with maximum intensity at a wavelength of 614 nm, is shown not to vary strongly with temperature (293-383 K). The decay constant of the phosphorescence, while independent of ambient pressure, decreases by approximately 12 µs/K between 323 and 373 K, with the base level of the decay constant dependent on the used solvent. The complex does not luminesce in the gas or solid state, meaning only the liquid phase is visualized, even in an evaporating spray. By using an internally excited spray containing the phosphorescent complex, the effect of vaporization is shown through the decrease in measured intensity over the length of the spray, together with droplet size measurements using interferometric particle imaging. This study shows that LIP, using the Eu-TTA-TOPO complex, can be used with different solvents, including diesel surrogates. Furthermore, it can be easily handled and used in sprays to investigate spray breakup and evaporation.

Belowground induction by Delia radicum or phytohormones affect aboveground herbivore communities on field-grown broccoli.

Induced plant defence in response to phytophagous insects is a well described phenomenon. However, so far little is known about the effect of induced plant responses on subsequently colonizing herbivores in the field. Broccoli plants were induced in the belowground compartment using (i) infestation by the root-herbivore Delia radicum, (ii) root application of jasmonic acid (JA) or (iii) root application of salicylic acid (SA). The abundance of D. radicum and six aboveground herbivores displaying contrasting levels of host specialization were surveyed for 5 weeks. Our study showed that the response of herbivores was found to differ from one another, depending on the herbivore species, its degree of specialization and the root treatment. The abundance of the root herbivore D. radicum and particularly the number of emerging adults was decreased by both phytohormone treatments, while the number of D. radicum eggs was increased on conspecific infested plants. The root infestation exhibited moderate effects on the aboveground community. The abundance of the aphid Brevicoryne brassicae was strongly increased on D. radicum infested plants, but the other species were not impacted. Root hormone applications exhibited a strong effect on the abundance of specialist foliar herbivores. A higher number of B. brassicae and Pieris brassicae and a lower number of Plutella xylostella were found on JA treated plants. On SA treated plants we observed a decrease of the abundance of B. brassicae, Pi. rapae, and P. xylostella. Surprisingly, generalist species, Mamestra brassicae and Myzus persicae were not affected by root induction treatments. Finally, root treatments had no significant effect on either glucosinolate (GLS) profiles of the heads or on plant quality parameters. These results are discussed from the perspective of below- aboveground interactions and adaptations of phytophagous insects to induced plant responses according to their trophic specialization level.

Molecular tagging velocimetry in turbulence using biacetyl.

We evaluate various molecular tagging velocimetry (MTV) techniques for application in turbulent flows of gases where the smallest length scales must be resolved. We argue that tracer diffusion dictates the use of large complex molecules and discuss a few candidate molecules. The accuracy of MTV is determined by the profile of written lines which widen due to molecular dynamics, including both diffusion and chemical reaction. We evaluate these profiles for tagging with phosphorescing biacetyl molecules, which is a commonly used probe in MTV. For relatively large laser power, these profiles are determined not by molecular diffusion, but by the triplet-triplet annihilation reaction of excited biacetyl molecules. We identify a new reaction pathway, and present a model for the observed line shapes. The rapid widening of tagged lines of biacetyl molecules due to chemical reaction restricts this MTV technique to large-scale turbulent motion in gases of comparable molecular weight.

Spectral narrowing in coherent Rayleigh-Brillouin scattering.

Coherent Rayleigh-Brillouin scattering is a four-wave mixing technique that provides information on various physical properties of the scattering medium in the spectral domain. Being based on density gratings generated by dipole forces, the method requires two pump beams of sufficient spectral width to span the full response bandwidth of the scattering medium. We provide experimental data on the scattered spectrum as a function of the coherence between the two pump beams and derive the corresponding pump beam spectrum. We argue that all experiments on coherent Rayleigh-Brillouin scattering to date, have, in fact, been performed in the incoherent regime and show that orders of magnitude in scattering efficiency are to be expected when the experiments are performed with bandwidth-limited picosecond laser pulses.

Coherent Rayleigh-Brillouin scattering measurements of bulk viscosity of polar and nonpolar gases, and kinetic theory.

We investigate coherent Rayleigh-Brillouin spectroscopy as an efficient process to measure the bulk viscosity of gases at gigahertz frequencies. Scattered spectral distributions are measured using a Fizeau spectrometer. We discuss the statistical error due to the fluctuating mode structure of the used pump laser. Experiments were done for both polar and nonpolar gases and the bulk viscosity was obtained from the spectra using the Tenti S6 model. Results are compared to simple classical kinetic models of molecules with internal degrees of freedom. At the extremely high (gigahertz) frequencies of our experiment, most internal vibrational modes remain frozen and the bulk viscosity is dominated by the rotational degrees of freedom. Our measurements show that the molecular dipole moments have unexpectedly little influence on the bulk viscosity at room temperature and moderate pressure.

Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety symptoms are associated with polydrug, not ecstasy, use.

Although previous studies have examined anxiety and depression in ecstasy (+/-3,4-methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms are associated specifically with ecstasy or with polydrug use in general. We compared mean symptomatology and clinically significant symptoms in 45 ecstasy polydrug, 48 cannabis polydrug and 40 legal drug users, who completed standardised self-report anxiety and depression symptom measures. We further examined whether group differences were secondary to increased somatic symptom reporting, which may reflect acute/subacute drug effects. Anxiety and depression scores were higher in polydrug than legal drug users, with no difference between ecstasy and cannabis groups. There was no difference in numbers meeting criteria for clinically significant depression or 'moderate' or 'severe' anxiety, but the polydrug group contained more individuals reporting at least 'mild' anxiety symptoms than the legal drug control. Multivariate analyses indicated that anxiety alone was sufficient to discriminate groups. Polydrug users reported more somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy polydrug users may be associated with polydrug rather than ecstasy use. Higher ratings in polydrug users appear to be secondary to increased somatic symptom reporting, suggesting possible impacts of drug effects on symptom endorsement.

Unawareness and undertreatment of asthma: follow-up in a different geographic area in Denmark.

BACKGROUND: Early detection and treatment of asthma is important to minimize morbidity and healthcare costs. The objective of this study was to investigate asthma awareness and management in a western society. METHODS: In a random sample of 10 400 subjects aged 14-44 years, 686 (6.6%) reported symptoms of asthma in a standardized screening questionnaire. All 686 were evaluated by respiratory specialists and diagnosed by history, symptoms, lung function tests, bronchial challenges and allergy testing. Of these 686 participants, 69 (10%) had asthma alone, 205 (30%) had rhinitis alone and 217 (32%) had both asthma and rhinitis; 195 (28%) had nonasthmatic respiratory reports. RESULTS: Awareness of asthma was found among 163 (57%) of the 286 asthmatics, and 204 (95%) had doctor-diagnosed rhinitis as well. In a multivariate regression analysis, comorbidity with rhinitis (beta = 0.489, P < 0.001), smoking (beta = -0.116, P < 0.01), doctor-diagnosed bronchitis (beta = 0.086, P < 0.05), and earlier emergency visits at hospital (beta = 0.147, P < 0.001) was significantly associated with awareness. A difference in awareness was found between those who had asthma and rhinitis (62.2%) and those who had asthma alone (40.6%) (P < 0.01). Inhaled corticosteroids (ICS) were used by 27% of those with asthma, including 12% who used both ICS and long-acting beta-agonist. CONCLUSIONS: More than half of the persons with asthma were aware of their disorder; and the awareness was more likely in those with comorbidity of rhinitis. In general, asthma management was inadequate.

How plants cope with biotic interactions.

In their natural environment, plants interact with many different organisms. The nature of these interactions may range from positive, for example interactions with pollinators, to negative, such as interactions with pathogens and herbivores. In this special issue, the contributors provide several examples of how plants manage both positive and negative biotic interactions. This review aims to relate their findings to what we know about the complex natural environments in which plants have evolved. Molecular analyses of plant genomes and expression profiles have shown how intricately plants may regulate responses to single or multiple biotic interactions. Plant responses are fine-tuned by signalling hormone interactions. When multiple organisms interact with a single plant this may result in antagonistic or synergistic effects. The emerging fields of ecogenomics and metabolomics undoubtedly will refine our understanding of the multilayered regulation that plants use to manage relationships with their biotic environment. However, we can only understand why plants have such an intricate regulatory apparatus if we consider the ecological context of plant biotic interactions.

Laser-induced fluorescence of NCN in low and atmospheric pressure flames.

The cyanonitrene radical, NCN, is detected by laser-induced fluorescence in laminar, adiabatic, flat phi=1.3 methane-air flames at 200 hPa and atmospheric pressure. Laser excitation of the A approximately 3Piu(020)-X approximately 3Sigmag-(000) band at 317 nm allows off-resonant fluorescence to be detected at 326 nm. Excitation and dispersed fluorescence spectra are presented, as well as profiles of NCN and CH versus height above burner.

Why plant volatile analysis needs bioinformatics--detecting signal from noise in increasingly complex profiles.

Plant volatile analysis may be the oldest form of what now is called plant "metabolomic" analysis. A wide array of volatile organic compounds (VOCs), such as alkanes, alcohols, isoprenoids, and esters, can be collected simultaneously from the plant headspace, either within the laboratory or in the field. Increasingly faster and more sensitive analysis techniques allow detection of an ever-growing number of compounds in decreasing concentrations. However, the myriads of data becoming available from such experiments do not automatically increase our ecological and evolutionary understanding of the roles these VOCs play in plant-insect interactions. Herbivores and parasitoids responding to changes in VOC emissions are able to perceive minute changes within a complex VOC background. Plants modified in genes involved in VOC synthesis may be valuable for the evaluation of changes in plant-animal interactions compared to tests with synthetic compounds, as they allow changes to be made within the context of a more complex profile. We argue that bioinformatics is an essential tool to integrate statistical analysis of plant VOC profiles with insect behavioural data. The implementation of statistical techniques such as multivariate analysis (MVA) and meta-analysis is of the utmost importance to interpreting changes in plant VOC mixtures. MVA focuses on differences in volatile patterns rather than in single compounds. Therefore, it more closely resembles the information processing in insects that base their behavioural decisions on differences in VOC profiles between plants. Meta-analysis of different datasets will reveal general patterns pertaining to the ecological role of VOC in plant-insect interactions. Successful implementation of bioinformatics in VOC research also includes the development of MVA that integrate time-resolved chemical and behavioural analyses, as well as databases that link plant VOCs to their effects on insects.

Above- and below-ground terpenoid aldehyde induction in cotton, Gossypium herbaceum, following root and leaf injury.

Studies on induced defenses have predominantly focused on foliar induction by above-ground herbivores and pathogens. However, roots are attacked by as many if not more phytophages than shoots, so in reality plants are exposed to above- and below-ground attack. Here, we report effects of foliar and/or root damage on terpenoid aldehyde accumulation in cotton (Gossypium herbaceum). Using HPLC, we analyzed concentrations of individual terpenoid aldehydes in foliage and root tissue. In undamaged plants, terpenoid aldehydes were concentrated in young immature main leaves. Concentrations in side leaves, branching from the main leaves, did not differ among leaf position. Above-ground feeding by Spodopterta exigua larvae on a mature leaf enhanced terpenoid concentrations in immature leaves but not in the damaged leaf. In particular, concentrations of hemigossypolone and the heliocides 1 and 4 were enhanced following herbivory. Root herbivory by wireworms (Agriotes lineatus) also resulted in an increase in terpenoid levels in the foliage. In contrast with foliar herbivory, both immature and mature leaves were induced. However, the level of induction after root herbivory was much lower compared to foliar herbivory. Plants exposed to root herbivory also had significantly higher levels of terpenoid aldehydes in root tissue, while no such effect was found following foliar herbivory. Plants exposed to both root and foliar herbivory appeared to induce primarily above-ground at the cost of below-ground defense. The implications for above- and below-ground Mutitrophic interactions are discussed.

Ontogeny constrains systemic protease inhibitor response in Nicotiana attenuata.

Protease inhibitors (PIs) are plant compounds that can inhibit proteases of mammal, insect, or pathogen origin and are frequently induced by mechanical wounding, insect feeding, or pathogen infection. Nicotiana attenuata is a species that induces nicotine, volatiles, and phenolics in response to damage. Here we examine the distribution of PIs in N. attenuata to determine if they are part of the induced response in this species and if this response is ontogenetically constrained. We found that N. attenuata shoot extracts inhibited trypsin (Tryp) and chymotrypsin (Chym) activities, while root extracts inhibited Tryp, Chym, and the bacterial protease subtilisin (Sub). The highest TrypPI levels were found at midday in the source-sink transition leaf, while older or younger leaves contained lower TrypPI levels and did not show significant diurnal fluctuations. Rosette plants, bolting plants, and flowering plants all contained TrypPIs in leaves, stems, and flowers, while seed capsules, seeds, and young seedlings did not contain any PIs. PIs in N. attenuata rosette plants were induced by Manduca sexta larval feeding, methyl jasmonate (MeJA) treatment, wounding, and application of M. sexta oral secretion and regurgitant. The response to MeJA application was stronger and longer lasting than to mechanical wounding. The direction and magnitude of the systemic response to mechanical wounding or larval damage depended on the age of the leaf that was damaged and the frequency of wounding. The systemic signal for TrypPI induction appears to follow source-sink relations in the plant and to be regulated by the octadecanoid pathway. Interestingly, by the time plants reach the flowering stage, they had lost the ability to increase PI levels after MeJA treatment. We concluded that plant ontogeny constrains both constitutive and inducible PI production in N. attenuata.

Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population.

OBJECTIVES: To examine various pre-, peri-, and neonatal factors in autistic participants and in pervasive developmental disorder-not otherwise specified (PDD-NOS) participants and to compare the incidence of each factor to that of the normal population. METHODS: Seventy-four participants (66 males, 8 females) were diagnosed with autism at 2.5 through 4 years of age using the most accurate and up-to-date methods, including the Diagnostic and Statistical Manual of Mental Disorders and the Autism Diagnostic Interview-Revised. At age 5, all participants were reevaluated using the Diagnostic and Statistical Manual of Mental Disorders, the Autism Diagnostic Interview-Revised, the Childhood Autism Rating Scale, and the Autism Diagnostic Observation Schedule-Revised, resulting in 61 autistic and 13 PDD-NOS participants. Twenty-eight pre-, peri-, and neonatal factors were examined in these 2 groups using both medical records and parental interviews. Incidences were compared with those of the US population as reported in the Report of Final Natality Statistics, 1995. This grand scale population group was used to closely approximate comparison to a normal, unbiased population. Results were analyzed using the binomial probability test, with a P value of <.05, constituting a significant difference in incidence. A Bonferroni correction was applied to the data to adjust for the number of factors investigated. RESULTS: Although most of the factors showed comparable incidences between the index and control groups, several factors showed statistically significant differences. Following the Bonferroni correction, the autism group was found to have a significantly higher incidence of uterine bleeding, a lower incidence of maternal vaginal infection, and less maternal use of contraceptives during conception when compared with the general population. Similarly, the PDD-NOS group showed a higher incidence of hyperbilirubinemia when compared with the general population. CONCLUSIONS: The results of this study support previous findings suggesting a consistent association of unfavorable events in pregnancy, delivery, and the neonatal phase and the pervasive developmental disorders. However, interpretation of the meaningfulness of these results is difficult, as the specific complications that carried the highest risk of autism and PDD-NOS represented various forms of pathologic processes with no presently apparent unifying feature. Additional studies are needed to corroborate and strengthen these associations, as well as to determine the possibility of an underlying unifying pathological process. This study's analysis of obstetric and neonatal complications in combination with the use of participants diagnosed at an early age provides some interesting concepts to consider. Perhaps future research will confirm certain pre-, peri-, and neonatal associations that could be used to generate a high-risk historical profile with which to use in conjunction with currently employed diagnostic tools. This may, in turn, help to determine the reliability of a diagnosis of autism in younger children, leading to earlier intervention and assistance for an improved outcome in long-term functionality and quality of life.

Nitric oxide flow tagging in unseeded air.

A scheme for molecular tagging velocimetry is presented that can be used in air flows without any kind of seeding. The method is based on the local and instantaneous creation of nitric oxide (NO) molecules from N(2) and O(2) in the waist region of a focused ArF excimer laser beam. This NO distribution is advected by the flow and can be visualized any time later by laser-induced fluorescence in the gamma bands. The creation of NO is confirmed by use of an excitation spectrum. Two examples of the application of the new scheme for air-flow velocimetry are given in which single laser pulses are used for creation and visualization of NO.

Induced responses in Nicotiana attenuata affect behavior and growth of the specialist herbivore Manduca sexta.

Many plants employ induced responses against generalist herbivores. Specialist herbivores, however, may employ several mechanisms to overcome the negative effects of induced plant defenses. Here we test how the behavior and development of specialist Manduca sexta larvae are affected by induced responses in their natural host plant Nicotiana attenuata. On a spatial scale relevant to both the plant and the herbivore, we first determined how methyl jasmonate (MeJA)-induced responses, such as increased nicotine production, affect the tendency of larvae to leave induced plants. When larvae were allowed to move between two plants planted in one pot, they left an MeJA-treated plant faster than a control plant. When both plants in the pot were MeJA-treated, the larvae developed more slowly than when both plants were uninduced, or when the larvae had the opportunity to move to an uninduced neighbor. The sooner larvae moved from an MeJA-treated plant to an untreated neighbor, the larger the body mass they attained. This demonstrates that M. sexta larvae can compensate behaviorally for the deleterious effects of induced plant responses. These effects were observed in plants grown under both low and high N supply rates, though the effects were more pronounced under high N. To examine the consequences of the timing and the direction of the host plant switching behavior for larval development, neonate larvae were fed leaves excised from induced and uninduced plants. Larvae confined to MeJA-treated leaves had higher mortality rates and grew slower than larvae fed only control leaves. This demonstrates that MeJA-induced responses decrease growth and development of specialist herbivores that do not have the behavioral option of moving to an uninduced plant. The sooner the larvae were switched to MeJA-treated leaves, the slower their development compared to larvae fed only uninduced leaves. In contrast, the sooner larvae fed MeJA-treated leaves were switched to control leaves, the faster they developed. Again the effects of MeJA treatment were stronger in plants grown under high N supply. We propose that induced plants growing in close competition with an uninduced conspecific may offset the fitness costs of these induced responses and perhaps obtain a fitness benefit by motivating herbivores to move to their neighboring competitors.

Methods to correct planar laser-induced fluorescence distributions for local nonuniform laser attenuation.

Planar laser-induced fluorescence is often used to obtain two-dimensional density distributions of specific molecules in reactive or nonreactive flows. In opaque environments, such as sooty flames or dusty air flows, the laser intensity decrease over the field of view must be taken into account. We describe two methods to determine the local extinction factor, and, from that, the local laser intensity. Both methods are based on elastic light scattering, one of which employs two elastic light scattering images, recorded simultaneously from the same probe volume, but illuminated from opposite directions. Although exact in principle, this method requires considerable experimental expenditure, and for this reason a more approximate method by use of only a single elastic scattering image is described as well. The results of both methods, applied to combustion diagnostics in an optically accessible Diesel engine, are compared.

Two-dimensional multispecies imaging of a supersonic nozzle flow.

Raman imaging is shown to be a very suitable technique for simultaneous density mapping of different species in dry air and N(2) supersonic nozzle flows. The salient features of Raman scattering are its molecular sensitivity and the fact that it can be spectrally separated from strong reflections and Mie scattering. We collected Raman images of both N(2) and O(2) concurrently by imaging the flow through an imaging spectrograph with a broad entrance slit onto a CCD camera. The main advantage of this method is that different species can be imaged under exactly the same flow conditions.

Generation of 224-nm radiation by stimulated Raman scattering of ArF excimer laser radiation in a mixture of H2 and D2.

Raman shifting of tunable ArF excimer laser radiation in a mixture of H(2) and D(2) produces tunable radiation in the 224-nm region as a result of Stokes shifting the frequency of the fundamental radiation (193 nm) once in both H(2) and D(2). At a total pressure of 25 bars, a 19% H(2) in D(2) mixture is found to provide a maximum conversion efficiency (2.5%) to the 224-nm range. Both fundamental and 224-nm radiation were used to record laser-induced fluorescence excitation spectra of nitric oxide produced in an oxyacetylene flame. From the excitation spectra, we determined the tuning range of the 224-nm radiation to be 270 cm(-1) with a linewidth of 0.9 cm(-1), which is similar to the fundamental laser radiation. We derived the exact Raman shift of the generated radiation by comparing both excitation spectra which was found to be 7142.3(5) cm(-1).