Acute sensitivity of the killifish Nothobranchius furzeri to a combination of temperature and reference toxicants (cadmium, chlorpyrifos and 3,4-dichloroaniline)

Abstract

Aquatic organisms of inland waters are often subjected to a combination of stressors. Yet, few experiments assess mixed stress effects beyond a select group of standard model organisms. We studied the joint toxicity of reference toxicants and increased temperature on the turquoise killifish, Nothobranchius furzeri, a promising model for ecotoxicological research due to the species' short life cycle and the production of drought-resistant eggs. The acute sensitivity of the larval stage (2dph) to three compounds (cadmium, 3,4-dichloroaniline and chlorpyrifos) was tested in combination with a temperature increase of 4 °C, mimicking global warming. Dose-response relationships were used to calculate 96h-LC₅₀ of 0.28 mg/L (24 °C) and 0.39 mg/L (28 °C) for cadmium, 96h-LC₅₀ of 9.75 mg/L (24 °C) and 6.61 mg/L (28 °C) for 3,4-dichloroaniline and 96h-LC₅₀ of 15.4 μg/L (24 °C) and 14.2 μg/L (28 °C) for chlorpyrifos. After 24 h of exposure, the toxicity of all tested compounds was exacerbated under increased temperature. Furthermore, the interaction effect of cadmium and temperature could be predicted by the stress addition model (SAM). This suggests the applicability of the model for fish and at the same time indicates that the model could be suitable to predict effects of temperature-toxicant interactions.

Identifying external nutrient reduction requirements and potential in the hypereutrophic Lake Taihu Basin, China

Abstract

Reducing external nutrient loads is the first step for controlling eutrophication. Here, we identified external nutrient reduction requirements and potential of strategies for achieving reductions to remediate a eutrophic water body, Lake Taihu, China. A mass balance approach based on the entire lake was used to identify nutrient reduction requirements; an empirical export coefficient approach was introduced to estimate the nutrient reduction potential of the overall program on integrated regulation of Taihu Lake Basin (hereafter referred to as the "Guideline"). Reduction requirements included external total nitrogen (TN) and total phosphorus (TP) loads, which should be reduced by 41–55 and 25–50%, respectively, to prevent nutrient accumulation in Lake Taihu and to meet the planned water quality targets. In 2010, which is the most seriously polluted calendar year during the 2008–2014 period, the nutrient reduction requirements were estimated to be 36,819 tons of N and 2442 tons of P, and the potential nutrient reduction strategies would reduce approximately 25,821 tons of N and 3024 tons of P. Since there is a net N remaining in the reduction requirements, it should be the focus and deserves more attention in identifying external nutrient reduction strategies. Moreover, abatement measures outlined in the Guideline with high P reduction potential required large monetary investments. Achieving TP reduction requirement using the cost-effective strategy costs about 80.24 million USD. The design of nutrient reduction strategies should be enacted according to regional and sectoral differences and the cost-effectiveness of abatement measures.

Dosage adjustments in patients with psoriasis on adalimumab: a retrospective chart review

Abstract

Adalimumab is a well-established treatment for chronic plaque psoriasis. While many clinical trials have shown its efficacy, few studies have looked at deviations from labeled dosing in the real-world setting.¹ The aim of this study was to determine the frequency of off-label dosing in patients with psoriasis on adalimumab and the reasons for these deviations.

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Patch testing in facial dermatitis using Chinese Baseline Series (60 allergens) and Cosmetic Series (58 allergens)

Abstract

Facial dermatitis (FD) is a common problem encountered in clinical practice. It effects patients' self-esteem and quality of life. Mild reactions such as itching, pricking, dryness can occur in more than 10% of patients[1]. Recurrence is common in FD. The cause of FD is often difficult to determine. Metals, cosmetics, air pollution and physical factors such as wind or changes in temperature and humidity in the environment may all contribute to the development of FD[2]. Patch test is useful in establishing the identification of FD[1,2]. The present study was carried out to determine the incidence and role of contact allergy in FD, using the Chinese Baseline Series and Cosmetic Series.

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The influence of exposome on acne

Abstract

Background

Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome.

Aim

to assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome.

Methods

two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review.

Results

acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified in the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed.

Conclusion

Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.

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Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in positron emission tomography-computer tomography and tumor volume, cytological activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is a rare malignant neuro-endocrine tumor of the skin that shows aggressive behavior and has a high tendency for local recurrence and lymph node or distant metastasis.¹ Recently, some reports have stated that 18-fluorodeoxyglucose positron emission tomography-computer tomography (FDG PET-CT) is more useful than conventional CT.^{2, 3} However, the utility of FDG PET-CT for determining the proliferative or metabolic activity of MCC is unclear. In this study, we investigated the correlation between FDG uptake and proliferative of metabolic activity as revealed by PET-CT imaging with Ki-67 immunological staining or GLUT-1 immunological staining in 10 cases of MCC. In addition, we tested the correlation between FDG uptake and tumor volume.

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Dissection of a circulating CD3+CD20+ T-cell subpopulation in patients with psoriasis

Summary

CD3⁺CD20⁺ T cells are a population of CD3⁺ T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. Here, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3⁺CD20⁺ T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3⁺ T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors. Circulating CD3⁺CD20⁺ T cells in patients with psoriasis were enriched in CD4⁺ cells and displayed an activated effector phenotype, for these cells contained less CD45RA⁺ naïve and CCR7⁺ cells with increased activity than those of CD3⁺ T cells lacking CD20. In addition, compared with healthy donors, circulating CD3⁺CD20⁺ T cells in patients with psoriasis produced more cytokines IL-17A, TNF-α and IL-21, but not IL-4 and IFN-γ. Furthermore, a significant positively correlation was found between the levels of IL-17A, TNF-α and IL-21-production CD3⁺CD20⁺ T cells with Psoriasis Area and Severity Index scores. Our findings suggest that CD3⁺CD20⁺ T cells may play a role in the pathogenesis of psoriasis. This article is protected by copyright. All rights reserved.

The CDK inhibitor Purvalanol A Induces Neutrophil Apoptosis and Increases the Turnover Rate of Mcl-1: Potential role of p38-MAPK in Regulation of Mcl-1 Turnover

Abstract

Human neutrophils are terminally-differentiated cells that do not replicate and yet express a number of enzymes, notably cell cycle-dependent kinases (CDKs) that are normally associated with control of DNA synthesis and cell cycle progression. In neutrophils, CDKs appear to function mostly to regulate apoptosis, although the mechanisms by which they regulate this process are largely unknown. Here we show that the CDK2 inhibitor, Purvalanol A induces a rapid decrease in Mcl-1 levels in human neutrophils and peripheral blood mononuclear cells (PBMCs), but only induces apoptosis in neutrophils which are dependent on expression on this protein for survival. This rapid decrease in cellular Mcl-1 protein levels was due to a Purvalanol A-induced decrease in stability, with the half-life of the protein decreasing from approximately 2h in control cells to just over 1h after addition of the CDK2 inhibitor: it also blocked the GM-CSF dependent stabilisation of Mcl-1. Purvanalol A blocked GM-CSF stimulated activation of Erk and STAT3, and stimulated an additive activation of Akt with GM-CSF. Purvalanol A alone stimulated a rapid and sustained activation of p38-MAPK and the pan p38-MAPK inhibitor, BIRB796 partly blocked the Purvalanol A-induced apoptosis and Mcl-1 loss. These novel effects Purvalanol A may result, at least in part, from blocking GM-CSF mediated Erk activation. In addition, we propose that Purvalanol A-induced activation of p38-MAPK is, at least in part, responsible for its rapid effects on Mcl-1 turnover and acceleration of neutrophil apoptosis. This article is protected by copyright. All rights reserved.

Measurement of Typhim Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency

ABSTRACT

Vaccine specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, maybe an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multicentre study describing the analytical and clinical performance of a Typhi Vi IgG ELISA calibrated to an affinity purified Typhi Vi IgG preparation. Intra- and inter-assay imprecision were low and the assay was linear between 7.4-574 U/mL (Slope=0.99-1.00; R²>0.99). 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations >7.4U/mL, the concentration range was 7.7-167 U/mL. In antibody deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were <25 U/mL. In vaccinated normal healthy volunteers, the median concentration post vaccination was 107 U/mL (range 31-542U/mL). 8/8 (100%) had post vaccination concentration increases of at least 3-fold and 6/8 (75%) of at least 10-fold. In an antibody deficient population (n=23), only 30% had post vaccination concentration increases of at least 3-fold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies. This article is protected by copyright. All rights reserved.

Ok, thanks! A new mutualism between Chlamydomonas and Methylobacteria facilitates growth on amino acids and peptides

Abstract

Nitrogen is a key nutrient for land plants and phytoplankton in terrestrial and aquatic ecosystems. The model alga Chlamydomonas reinhardtii can grow efficiently on several inorganic nitrogen sources (e.g. ammonium, nitrate, nitrite) as well as many amino acids. In this study, we show that Chlamydomonas is unable to use proline, hydroxyproline, and peptides that contain these amino acids. However, we discovered that algal growth on these substrates is supported in association with Methylobacterium spp., and that a mutualistic carbon-nitrogen metabolic exchange between Chlamydomonas and Methylobacterium spp. is established. Specifically, the mineralization of these amino acids and peptides by Methylobacterium spp. produces ammonium that can be assimilated by Chlamydomonas, and CO₂ photosynthetically fixed by Chlamydomonas yields glycerol that can be assimilated by Methylobacterium. As Chlamydomonas is an algal ancestor to land plants and Methylobacterium is a plant growth-promoting bacterium (PGPB), this new model mutualism may facilitate insights into the ecology and evolution of plant-bacterial interactions and design principles of synthetic ecology.

The solute transport profile of two Aza-guanine transporters from the Honey bee pathogen Paenibacillus larvae

Abstract

Two nucleobase transporters encoded in the genome of the Honey bee bacterial pathogen Paenibacillus larvae belong to the azaguanine-like transporters and are referred to as PlAzg1 and PlAzg2. PlAzg1 & 2 display significant amino acid sequence similarity, share predicted secondary structures and functional sequence motifs with two Escherichia coli nucleobase cation symporter 2 (NCS2) members; adenine permease (EcAdeP) and guanine-hypoxanthine permease EcGhxP. However, similarity does not define function. Heterologous complementation and functional analysis using nucleobase transporter deficient Saccharomyces cerevisiae strains revealed that PlAzg1 transports, adenine, hypoxanthine, xanthine and uracil, while PlAzg2 transports adenine, guanine, hypoxanthine, xanthine, cytosine and uracil. Both PlAzg1 & 2 display high affinity for adenine with K_m of 2.95 ± 0.22 μM and 1.92 ± 0.22 μM, respectively. These broad nucleobase transport profiles are in stark contrast to the narrow transport range observed for EcAdeP (adenine) and EcGhxP (guanine and hypoxanthine). PlAzg1 & 2 are similar to eukaryotic Azg-like transporters in that they share a broad solute transport profile, particularly the fungal Aspergillus nidulans AzgA (that transports adenine, guanine and hypoxanthine) and plant AzgA transporters from Arabidopsis thaliana and Zea mays (that collectively move adenine, guanine, hypoxanthine, xanthine, cytosine and uracil).

Individual variation of natural D. melanogaster associated bacterial communities

Abstract

D. melanogaster has become an important model organism to study host-microbe interaction in the laboratory. However, the natural microbial communities that are associated with D. melanogaster have received less attention. Especially, information on inter-individual variation is still lacking because most studies so far have used pooled material from several flies. Here, we collected bacterial 16S rRNA gene community profiles from a set of 32 individuals from a single population. We simulated pools from the individual data (i) to assess how well the microbiome of a host population is represented by pools, and (ii) to compare variation of Drosophila microbiomes within and between populations. Taxon richness was increased in simulated pools, suggesting that pools paint a more comprehensive picture of the taxa associated with a host population. Furthermore, microbiome composition varied less between pools than between individuals, indicating that differences even out in pools. Variation in microbiome composition was larger between populations than between simulated pools from a single population, adding to the notion that there are population-specific effects on the Drosophila microbiome. Surprisingly, samples from individuals clustered into two groups, suggesting that there are yet unknown factors that affect the composition of natural fly-associated microbial communities and need further research.

Osmotolerance of Dekkera bruxellensis and the role of two Stl glycerol-proton symporters

Abstract

Dekkera bruxellensis is important for lambic beer fermentation, but is considered a spoilage yeast in wine fermentation. We compared two D. bruxellensis strains isolated from wine and found that they differ in some basic properties including osmotolerance. The genomes of both strains contain two highly similar copies of genes encoding putative glycerol-proton symporters from the STL family which are important for yeast osmotolerance. Cloning of the two DbSTL genes and their expression in suitable osmosensitive S. cerevisiae mutants revealed that both identified genes encode functional glycerol uptake systems, but only DbStl2 has the capacity to improve the osmotolerance of S. cerevisiae cells.

Frontal fibrosing alopecia after antiandrogen hormonal therapy in a male patient

Abstract

An 82-year-old man with a prostate adenocarcinoma, started eight years before a treatment with oral bicalutamide 50 mg daily and subcutaneous goserelin 10,8 mg each three months, an antiandrogen and a LHRH analogue, respectively. The rest of his past medical history was unremarkable. A few months after starting with the treatment, he began with recession of the frontotemporal hairline also with hypopigmentation and atrophy of the areas of alopecia and loss of axillary and pubic hair (Figure 1). He did not present any clinical signs or patterns of male androgenetic alopecia. He denied having any siblings or kindreds with a scarring alopecia and therefore a familial FFA was excluded. Laboratory test showed low levels of prostate specific antigen (0,024ɥg/L) and undetectable free serum testosterone levels (<0,1 nmol/L). A biopsy on the scalp revealed a lichenoid lymphocitic inflammatory infiltrate, important fibrosis with loss of elastic fibers and hair follicle destruction (Figure 2,3). The clinical and histopathological features were consistent with frontal fibrosing alopecia. He is still having this treatment in order to prevent the progression of the prostate adenocarcinoma.

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A study of androgenic signs and disorders in Greek female patients with acne

Abstract

Acne represents an established cutaneous manifestation of hyperandrogenism (1). There are scarce studies of androgenic signs or disorders including polycystic ovary syndrome (PCOS), hirsutism, menstrual irregularities or androgenic alopecia, in patients with acne.

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A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species

Abstract

Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance of Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4,995 Cryptococcus isolates from 3,210 patients constituted this study; 248 (5.0%) of the isolates were from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of ≥64 μg/mL to define fluconazole resistance, 6 (21%) used ≥32 μg/mL, 11 (38%) used ≥16 μg/mL, and 1 (3%) used ≤20 μg/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval (CI): 6.7% - 17.6%) for all isolates (n=4,995). Mean fluconazole resistance was 10.6% (95% CI: 5.5% - 15.6%) for the incident isolates (n=4,747), and 24.1% (95% CI: -3.1% - 51.2%) for the relapse isolates (n=248). Of the 4,995 isolates, 936 (18.7%) had MICs above the ecological cut-off value. Fluconazole resistance appears to be an issue in Cryptococcus isolates from patients with relapses. It is unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for Cryptococcus spp.

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Enlarging tumor of the lateral chest wall in a 14-year-old boy

Ulcerative telangiectasia on the face and back of a 6-year-old girl with elevated antinuclear antibodies

Biosimilars and patient care

Atypical fibroxanthoma with prominent CD8-positive lymphocytic infiltration and diffuse expression of epithelial membrane antigen