Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response.

BACKGROUND: Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. METHODS: Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo-keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed. RESULTS: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = -0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo-keto reductases, or epoxide hydrolase protein expression. CONCLUSION: These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.

Impact of prolonged storage of clinical samples at 4°C on the recovery of dermatophytes by culture or PCR analysis.

Dermatophytes are common pathogens in superficial mycoses that are routinely identified by culture or PCR analysis of freshly collected skin, nail or hair specimens. Although clinical samples are normally processed without delay, practical or research issues may necessitate sample storage until later analysis. However, the influence of extended sample storage on the ability to recover fungi by culture vs. PCR analysis has not been specifically studied. Here, a total of 172 dermatological samples collected from 2013-2015 were examined before and after refrigerated storage at 4°C for 10.2-32.3 (mean 25.6) months. By culture, 35% of the dermatophyte-containing fresh samples remained positive at re-examination. At species level, only 19% of initially Trichophyton rubrum-positive samples yielded a positive result after refrigeration, whereas few samples containing Trichophyton violaceum, Microsporum canis or Microsporum audouinii remained culture-positive. Using PCR, 76% of dermatophyte DNA-positive fresh samples were still positive at re-analysis. Notably, 92% of the samples targeted by the T. rubrum DNA primer remained positive after storage. Hence, PCR analysis is more favourable than cultivation with regard to the detectability of dermatophytes in long-term refrigerated clinical samples.

Decoupling of female host plant preference and offspring performance in relative specialist and generalist butterflies.

The preference-performance hypothesis posits that the host plant range of plant-feeding insects is ultimately limited by larval costs associated with feeding on multiple resources, and that female egg-laying preferences evolve in response to these costs. The trade-off of either using few host plant species and being a strong competitor on them due to effective utilization or using a wide host plant range but being a poor competitor is further predicted to result in host plant specialization. This follows under the hypothesis that both females and offspring are ultimately favoured by utilizing only the most suitable host(s). We develop an experimental approach to identify such trade-offs, i.e. larval costs associated with being a host generalist, and apply a suite of experiments to two sympatric and syntopic populations of the closely related butterflies Pieris napi and Pieris rapae. These butterflies show variation in their level of host specialization, which allowed comparisons between more and less specialized species and between families within species. Our results show that, first, the link between female host preference and offspring performance was not significantly stronger in the specialist compared to the generalist species. Second, the offspring of the host plant specialist did not outperform the offspring of the generalist on the former's most preferred host plant species. Finally, the more generalized species, or families within species, did not show higher survival or consistently higher growth rates than the specialists on the less preferred plants. Thus, the preference and performance traits appear to evolve as largely separated units.

Reproductive isolation and patterns of genetic differentiation in a cryptic butterfly species complex.

Molecular studies of natural populations are often designed to detect and categorize hidden layers of cryptic diversity, and an emerging pattern suggests that cryptic species are more common and more widely distributed than previously thought. However, these studies are often decoupled from ecological and behavioural studies of species divergence. Thus, the mechanisms by which the cryptic diversity is distributed and maintained across large spatial scales are often unknown. In 1988, it was discovered that the common Eurasian Wood White butterfly consisted of two species (Leptidea sinapis and Leptidea reali), and the pair became an emerging model for the study of speciation and chromosomal evolution. In 2011, the existence of a third cryptic species (Leptidea juvernica) was proposed. This unexpected discovery raises questions about the mechanisms preventing gene flow and about the potential existence of additional species hidden in the complex. Here, we compare patterns of genetic divergence across western Eurasia in an extensive data set of mitochondrial and nuclear DNA sequences with behavioural data on inter- and intraspecific reproductive isolation in courtship experiments. We show that three species exist in accordance with both the phylogenetic and biological species concepts and that additional hidden diversity is unlikely to occur in Europe. The Leptidea species are now the best studied cryptic complex of butterflies in Europe and a promising model system for understanding the formation of cryptic species and the roles of local processes, colonization patterns and heterospecific interactions for ecological and evolutionary divergence.

Heterospecific courtship, minority effects and niche separation between cryptic butterfly species.

Species interacting in varied ecological conditions often evolve in different directions in different local populations. The butterflies of the cryptic Leptidea complex are sympatrically distributed in different combinations across their Eurasian range. Interestingly, the same species is a habitat generalist in some regions and a habitat specialist in others, where a sibling species has the habitat generalist role. Previous studies suggest that this geographically variable niche divergence is generated by local processes in different contact zones. By varying the absolute and relative densities of Leptidea sinapis and Leptidea juvernica in large outdoor cages, we show that female mating success is unaffected by conspecific density, but strongly negatively affected by the density of the other species. Whereas 80% of the females mated when a conspecific couple was alone in a cage, less than 10% mated when the single couple shared the cage with five pairs of the other species. The heterospecific courtships can thus affect the population fitness, and for the species in the local minority, the suitability of a habitat is likely to depend on the presence or absence of the locally interacting species. If the local relative abundance of the different species depends on the colonization order, priority effects might determine the ecological roles of interacting species in this system.

Do acetyl salicylic acid and terbutaline in combination increase the probability of a clinical pregnancy in patients undergoing IVF/ICSI?

The present study investigated if acetyl salicylic acid (ASA) and terbutaline in combination increased the clinical pregnancy rate in patients undergoing in vitro fertilisation (IVF)/intra-cytoplasmic sperm injection (ICSI). A randomised controlled trial was designed, in which 167 patients were randomised to taking ASA for 9 weeks after embryo transfer and terbutaline around the time of embryo transfer as adjuvant medication. A total of 112 patients were randomised to no adjuvant medication. The clinical pregnancy rate per controlled ovarian hyperstimulation was 30.5% in the intervention group and 42.0% in the control group. This difference was not statistically significant, and we conclude that ASA and terbutaline in combination do not increase the clinical pregnancy rate after IVF/ICSI treatment.

Nurses' views on ease of patient care in postoperative pain management.

The fentanyl HCl iontophoretic transdermal system (ITS) is a compact, needle-free, pre-programmed patient-controlled analgesic system that was developed to address limitations to existing therapies for postoperative pain management. A randomized, controlled trial was conducted in 11 European countries to evaluate the efficacy and safety of postoperative pain control using fentanyl ITS compared with a standard regimen of morphine provided by an intravenous patient-controlled analgesia (IV PCA) pump. This article summarizes results from Nurse Ease-of-Care Questionnaires which were completed to assess the convenience and ease of use of each pain management modality from the perspective of the nurse. Nurses' ratings of patient-care tasks associated with each pain management system were significantly more favourable for fentanyl ITS than for morphine IV PCA. These findings suggest that nurses consider fentanyl ITS to be easier to use than morphine IV PCA.

Trisomy 10 mosaicism and maternal uniparental disomy 10 in a liveborn infant with severe congenital malformations.

We report on a liveborn infant with trisomy 10 mosaicism combined with maternal uniparental heterodisomy for chromosome 10. The mosaicism 47,XY,+10/46,XY was found in five different tissues, including one blood sample, while cultured lymphocytes from two other blood samples showed a normal karyotype, 46,XY. DNA analysis with six PCR-based microsatellite markers demonstrated the trisomic cell line to be a result of maternal meiotic nondisjunction, and revealed maternal uniparental heterodisomy in the diploid cell line, suggesting that the formation of the diploid cell line was due to trisomy rescue. The boy had severe growth retardation, major dysmorphism, and malformations, and died at 37 days. We reviewed the previous nine reports of infants and fetuses with trisomy 10 mosaicism reported in the literature. We suggest that a common clinical syndrome can be defined comprising skull, jaw and ear abnormalities, cleft lip/palate, malformations of eyes, heart and kidneys, deformity of hands and feet, and most often death neonatally or in early infancy. The cytogenetic findings in the present patient demonstrate the importance of karyotyping more than one tissue, and not only lymphocytes, when a chromosomal aberration is strongly suspected.

LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge with Salmonella spp.

In the current study we examined the ability of a novel mucosal adjuvant, LT(R192G), to enhance the humoral and cellular immune responses against killed Salmonella spp. and to affect protection against lethal oral challenge with wild-type organisms. Mice orally immunized with killed S. dublin in conjunction with LT(R192G) were protected against lethal oral challenge and had higher IFN-gamma, IL-2 and IgG responses than did mice orally immunized with killed S. dublin alone which were not protected. This study demonstrates that the function of LT(R192G) in protection against typhoid-like disease is to upregulate/enhance the Th1 arm of the immune response against killed organisms. When used as a mucosal adjuvant, LT(R192G) enables the use of killed bacteria or viruses as vaccines by enhancing the overall humoral and cellular host immune response to these organisms, especially the Th1 arm of the immune response. These findings have significant implications for vaccine development and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines.

Comparison of indapamide and hydrochlorothiazide plus amiloride as a third drug in the treatment of arterial hypertension.

In a randomized, double-blind crossover trial, indapamide (IND) 2.5 mg and hydrochlorothiazide 25 mg + amiloride 2.5 mg (HCTZ + A) were found to be equally effective in reducing blood pressure (BP) in 13 patients with moderate to severe hypertension already receiving chronic treatment with a beta blocker and a vasodilatator (supine BP during run-in: 169/103 +/- 21/5 mmHg; on IND: 149/91 +/- 21/14 mmHg; on HCTZ + A 144/88 +/- 23/5 mmHg). Both drugs induced insignificant reductions in body weight, and no change in plasma volume was seen. Serum potassium was significantly reduced on both regimens--the values recorded on IND being significantly lower than those seen on HCTZ + A. Values below 3.0 mmol/l were found in two patients receiving IND, but no subjective side effects were reported. Hyperuricemia occurred with the same frequency on both regimens. It is concluded that IND, just like the thiazide diuretics, is useful as the third drug in patients needing triple drug therapy to control BP, but metabolic adverse effects are not avoided by the choice of this drug.