Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates

Background/Objectives

Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown.

Methods

In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM₁₀), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers'' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders.

Results

Mean (95%-CI) PM₁₀ exposure for the last 7 days of pregnancy was 18.3 (10.3–38.4 µg/m³). PM₁₀ exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found.

Conclusions

Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort.     

Identification of multiple HPV types on spermatozoa from human sperm donors

Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.     

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are-at least to some extent-nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline.     

Lentiviral gene transfer into the dorsal root ganglion of adult rats

Background

Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K⁺ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K_2P channels after peripheral axotomy in mammals.

Results

Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo.

Conclusions

In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.     

Transcranial magnetic stimulation intensities in cognitive paradigms

Background

Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain''s functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm.

Methods and Findings

Repetitive TMS (rTMS) was applied prior to a working memory task, either at the ‘fixed’ intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject''s MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects.

Conclusion

Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain.     

Temperature and resource availability may interactively affect over-wintering success of juvenile fish in a changing climate

The predicted global warming may affect freshwater systems at several organizational levels, from organism to ecosystem. Specifically, in temperate regions, the projected increase of winter temperatures may have important effects on the over-winter biology of a range of organisms and especially for fish and other ectothermic animals. However, temperature effects on organisms may be directed strongly by resource availability. Here, we investigated whether over-winter loss of biomass and lipid content of juvenile roach (Rutilus rutilus) was affected by the physiologically relatively small (2-5 °C) changes of winter temperatures predicted by the Intergovernmental Panel on Climate Change (IPCC), under both natural and experimental conditions. This was investigated in combination with the effects of food availability. Finally, we explored the potential for a correlation between lake temperature and resource levels for planktivorous fish, i.e., zooplankton biomass, during five consecutive winters in a south Swedish lake. We show that small increases in temperature (+2 °C) affected fish biomass loss in both presence and absence of food, but negatively and positively respectively. Temperature alone explained only a minor part of the variation when food availability was not taken into account. In contrast to other studies, lipid analyses of experimental fish suggest that critical somatic condition rather than critical lipid content determined starvation induced mortality. Our results illustrate the importance of considering not only changes in temperature when predicting organism response to climate change but also food-web interactions, such as resource availability and predation. However, as exemplified by our finding that zooplankton over-winter biomass in the lake was not related to over-winter temperature, this may not be a straightforward task.     

Differential detection of potentially hazardous Fusarium species in wheat grains by an electronic nose

Fungal infestation on wheat is an increasingly grave nutritional problem in many countries worldwide. Fusarium species are especially harmful pathogens due to their toxic metabolites. In this work we studied volatile compounds released by F. cerealis, F. graminearum, F. culmorum and F. redolens using SPME-GC/MS. By using an electronic nose we were able to differentiate between infected and non-infected wheat grains in the post-harvest chain. Our electronic nose was capable of distinguishing between four wheat Fusaria species with an accuracy higher than 80%.