Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicine for acute myeloid leukemia in elderly patients

Abstract

Background

The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion daunorubicin plus cytarabine (DA).

Patients and methods

Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m² BID days 1,3,5,7) plus mitoxantrone (10 mg/m² days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m² continuously days 1-7) plus daunorubicin (45 mg/m² days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.

Results

Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The CR rate after DA was 39% (95%-CI; 33-45) versus 55% (95%-CI; 49-61) after IMA (OR 1.89, p=0.001). The six-week early-death rate was 14% in both arms. Relapse-free survival (RFS) curves were superimposable in the first year, but separated afterwards, resulting in 3-year RFS rates of 29% versus 14% in the DA versus IMA arms, respectively (p=0.042). The median OS was 10 months in both arms (p=0.513).

Conclusion

The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate dose cytarabine in induction may improve curative treatment for elderly AML patients.

Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

Ann Oncol 2017; 28: 1339–1345 (doi: 10.1093/annonc/mdx075)

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Summary

Background

Hereditary factors are involved in the pathogenesis of atopic dermatitis (AD). However, AD-related gene variations are significantly different across ethnicities.

Aim

To identify mutations and single-nucleotide polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients with AD and compare the variations with those observed in nonatopic healthy controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD-related gene variants.

Methods

We carried out REBA to simultaneously detect variations in genes related to barrier or immune function, namely, FLG, SPINK5, KLK7, DEFB1, TNFα, KDR, FCER1A, IL4, IL5,IL5RA, IL9, IL10, IL12, IL12R, IL13 and IL18, from Korean patients with AD, and compared the variation to that in nonatopic healthy controls.

Results

The homozygous mutants of KLK7 and SPINK5-2475, and the heterozygous mutants of FLG 3321delA, SPINK5-1156, DEFB1, KDR, IL5RA, IL9 and IL12RB1 were significantly more frequent in AD. It has been predicted that the larger the number of gene variants, the higher the odds ratio of AD prevalence; however, we did not find any significant correlation between the number of gene variants and AD severity.

Conclusion

Using REBA, we identified more genetic variants that can predict AD occurrence. We also verified that REBA can be used to easily and accurately detect multiple AD-related gene variants simultaneously. In addition, we identified a correlation between KLK7 mutation and AD in Koreans, which is the first such report, to our knowledge.

RE: “IMPACT OF BLAST INJURY ON HEARING IN A SCREENED MALE MILITARY POPULATION”

A topical treatment containing heat-treated Lactobacillus johnsonii NCC 533 reduces Staphylococcus aureus adhesion and induces antimicrobial peptide expression in an in vitro reconstructed human epidermis model

Abstract

Staphylococcus aureus colonization is thought to contribute to the pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of cutaneous antimicrobial peptides (AMPs), which may explain their increased susceptibility to infections. Using an in vitro reconstructed human epidermis (RHE) model, we sought to determine whether topical application of a non-replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1), could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We found that application of HT La1 suspension to RHE samples reduced the binding of radiolabeled S. aureus by up to 74%. To investigate a potential effect of HT La1 on innate immunity, we analyzed the expression of nine AMP genes, including those encoding beta defensins and S100 proteins, following topical application of HT La1 in suspension or in a daily moisturizer lotion. Analyzed genes were induced by up to four-fold in a dose-dependent manner by HT La1 in suspension, and by up to 2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and immunohistochemical detection, we evaluated the expression and secretion of the AMPs hBD-2 and psoriasin, and determined that both proteins were induced by topical HT La1, particularly in the stratum corneum of the RHE. These findings demonstrate that a topically applied, non-replicating probiotic can modulate endogenous AMP expression and inhibit binding of S. aureus to an RHE model in vitro. Moreover, they suggest that a topical formulation containing HT La1 could benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus colonization.

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Post-transplant lymphoproliferative disease with features of cutaneous natural killer/T-cell lymphoma

Homeobox transcription factor DLX4 is not necessary for skin development and homeostasis

Abstract

Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal-less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its cis-linked gene Dlx3 during mouse development as well as in neonatal and adult skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs, digits, nose, hair follicle and in the basal and suprabasal layers of mouse interfollicular epidermis in neonatal and adult skin. We show that inactivation of Dlx4 in mice did not result in any overtly gross pathology. Skin development, homeostasis and response to TPA treatment was similar in mice with loss of Dlx4 compared to wild type counterparts.

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The Location and Boundaries of Consciousness: a Structural Realist Approach

Abstract

Despite the remarkable progress made in consciousness research during recent decades, there is still no sign of a general agreement about the location of its object. According to internalists, consciousness resides inside the brain. According to externalists, consciousness is partly constituted by elements or aspects of the environment. Internalism comports better with the existence of dreams, hallucinations and sensory imaging. Externalism seems to provide a more promising basis for understanding how we can experience the world and refer to the content of our consciousness. I argue that the framework of structural realism supports internalism and helps to reveal the reasons behind the apparent explanatory success of the externalist approach. More specifically, structural realism supports the view that the structure of our consciousness is always present in our neural processes and only sometimes (additionally) in an extended system that includes elements of the environment.

Nickel hypersensitivity following closure of atrial septal defect: A case report and review of the literature

Abstract

We present an unusual case where symptoms of headache and chest pain persisted for 3 years following the implantation of a septal occluder device for an atrial septal defect despite endothelialisation of the device. The patient was found to have nickel hypersensitivity on patch testing. Following the removal of the device the patient had complete resolution of headaches and chest pain up to 10 months post-explantation.

Rapid exacerbation of malignant melanoma during short-term discontinuation of vemurafenib

Cd and Cu accumulation, translocation and tolerance in Populus alba clone (Villafranca) in autotrophic in vitro screening

Abstract

The present study investigated accumulation, translocation and tolerance of autotrophic Populus alba clone "Villafranca" in response to excess concentrations of cadmium (Cd) and copper (Cu) provided to the plants. For this purpose, increasing concentrations of Cd (0, 5, 50 and 250 μM) and Cu (0, 5, 50, 250 and 500 μM) were administered to the growth medium in which micropropagated poplar plantlets were exposed to metal treatments for 15 days. Filter bags, instead of the conventional in vitro screening, were applied to improve the experimental design. Results showed that Cd and Cu increased in shoots and roots at increasing metal concentration in the medium. The highest Cd content was found in leaves, while the highest Cu content was found in roots. In "Villafranca", Cu showed toxic effects on the development of the seedlings, especially at the highest concentrations, reducing plant dry mass. However, the tolerance index (Ti) indicated good tolerance in this clone under exposure to excess metal concentrations, whereas plants had higher translocation factor (Tf). We recommend in vitro selection of tolerant genotypes, aimed at providing early indication on accumulation potentiality and tolerance capability in research on plant sensitivity to excess heavy metal concentrations.

A study through batch tests on the analytical determination and the fate and removal of methamphetamine in the biological treatment of domestic wastewater

Abstract

Methamphetamine (MET) is one of the most used illicit drugs in Europe and is recognized as one of the Emerging Organic Micropollutants. It is discharged into the sewerage system from different sources and then enters the wastewater treatment plants. The present study aimed at providing a better knowledge of the fate of MET through the wastewater treatment plants. The study addressed two different issues: (1) optimization of the analytical methods for MET determination in both liquid and sludge phases, focusing on the effects of potentially interfering substances and (2) investigation on the behaviour of MET in the biological treatment process, with specific concern for the biomass activity at different drug concentrations. Results of the study on issue 1 highlighted that the applied analytical method for MET determination (UPLC–MS/MS) is affected by the main components of wastewater for about 9–23%, which is comparable with the uncertainties of the method (about ± 28%). The method showed also to be repeatable and reliable (recovery > 75%; repeatability < 10–15%; bias uncertainty < 30%), and relatively easy-to-use. Therefore, it can be considered suitable for measurements on routine base in the WWTPs. Batch tests conducted to address issue 2 showed total removal of 84, 90, and 96% at 50, 100, and 200 ng/L initial MET concentration, respectively, for a contact time of 6 h. The removal process was mainly ascribed to the biological activity of both heterotrophic and autotrophic bacteria. The pseudo first-order kinetic model provided the best fitting of the experimental data of the overall biological processes at all the tested concentrations. Furthermore, the respirometric tests showed that MET does not induce any inhibition. Adsorption of MET on activated sludge was always very low.

Effects of air pollution on hospital visits for pneumonia in children: a two-year analysis from China

Abstract

Although the effect of air pollution on respiratory health has been identified, few studies can be available to evaluate the association of air pollution with hospital visits for children's pneumonia in China. To explore whether high concentrations of air pollutants (including PM_2.5, PM₁₀, NO₂, and SO₂) are related to hospital visits for pneumonia in children, we conducted a population-based time-series study in Ningbo, China, from January 1st, 2014 to November 1st, 2015. We used a generalized additive Poisson regression model to calculate risk ratios and 95% confidence intervals for the associations of air pollutants and hospital visits for pneumonia in children and found that these four pollutants were associated with the increased hospital visits for pneumonia in children (1.3% for PM2.5, 1.0% for PM10, 2.9% for NO₂, 5.0% for SO₂ per 10-μg/m³ increase in PM2.5, PM10, NO₂, and SO₂, respectively). Stronger associations were observed in the cold seasons and among children under 5 years.

Characterization and cancer risk assessment of VOCs in home and school environments in gran La Plata, Argentina

Abstract

Three areas are highlighted in Gran La Plata, Argentina: industrial, urban, and residential. In this work, the levels of volatile organic compounds (VOCs) in indoor air of homes and schools in those areas were analyzed, through the use of passive monitors. The study period is between 2007 and 2010. Higher levels of VOCs were found in homes and schools in the industrial zone, higher than the levels corresponding to urban and residential. Taking into account the relationship between indoor and outdoor levels of VOCs, they have ratios (I/O) between 1.5 and 10 are evidenced contributions of emission sources of VOCs both indoor and outdoor. Complementarily, we estimated the life time cancer risk (LCR) for benzene, styrene, trichloroethylene, and tetrachloroethylene in children who spend their time mostly in such indoor environments. The results show high LCR values for benzene, which exceed acceptable values for the US EPA.

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

Assessment of the general quality of sunscreen products available in Palestine and method verification of the sun protection factor using Food and Drug Administration guidelines

Summary

Background

Sunlight exposure affects all skin types causing skin tanning, burns or even skin cancer. Sunscreens were invented to prevent these outcomes by scattering or absorbing the UV light.

Aims

This study aimed to verify the effectiveness of Mansur method in SPF measurement and to find out how much reliable the labeled sun protection factor (SPF) value for the products that are imported to Palestine knowing that they are considered as cosmetics and they don't undergo tests by the Ministry Of Health (MOH).

Materials

In this research, sun protection factor (SPF) was determined for 16 commercially available sunscreen products using Mansur equation which was also validated; moreover sunscreen classification, product phase determination and pH measurement were also done.

Results

Sun protection factor values were mostly 50, 43.75% of the analyzed samples were close to the labeled SPF, 31.25% were under the labeled value, and 25% SPF value above the labeled value. All samples exhibited a pH close to skin pH. 62% of them were found to be O/W. Cosmetic companies and importers should focus on pediatric sunscreens, since only 12.5% are pediatric sunscreens.

Conclusions

Ministry Of Health should ask prove about the quality of an SPF value of sunscreens for final registration of these products. More instructions should be available on the label regarding the proper use especially, if they are not water proof.

Chronology of regional lymph node metastases in cutaneous melanoma: a model based on mitotic rate

Abstract

Recently, the MSLT-II¹ and DeCOG² clinical trials have failed to demonstrate a benefit for the lymphadenectomy vs. observation in the setting of a patient with positive sentinel lymph node biopsy. Therefore, it is expected in the short term an increase in the patients with a more conservative management and obviously, more regional recurrences.

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Sonochemical degradation of triclosan in water in a multifrequency reactor

Abstract

Degradation of triclosan (TCS) by multifrequency ultrasound (US) was studied at high and low frequencies. Frequency effect on initial degradation rates was analyzed, and an optimum frequency was found. Power density always has a positive effect on degradation rates over the whole equipment work range. A reaction mechanism similar to that proposed by Serpone resulted in a pseudo-linear model that fitted statistically better than the nonlinear model proposed by Okitsu. Pulsed US showed a positive effect on degradation rates; however, simultaneous analysis of the effect of power, frequency, pulse time, and silent time did not show a clear trend for degradation as a function of pulse US variables. According to these results and those for degradation in the presence of radical scavengers, it was concluded that US TCS degradation was taking place in the bubble/liquid interface. A toxicity test was conducted by Microtox®, showing a decrease in toxicity as TCS concentration decreased and increase in toxicity after total depletion of TCS. Eight possible degradation by-products were identified by GC-MS analysis, and a degradation pathway was proposed.

Topical Paromomycin for treating solitary mucosal leishmaniasis

Clinical features and management of schwannoma affecting the upper and lower lips

Abstract

Head and neck schwannomas comprise 25–40% of all schwannomas, with presentation on the lips as the rarest and most surgically complicated site for perioral tumors. A systematic literature review was conducted to include 21 cases of patients with schwannoma of the upper or lower lips. The majority of patients presented with a single, painless, well-encapsulated nodule on the upper or lower lips. The nodules were consistently slow-growing, with an average 29.3 months from symptom onset to clinical presentation. Most cases were complicated by profound cosmetic disfigurement as well as dysphagia, dysarthria, snoring, and/or sleep apnea. Overall, histological analysis was consistent with classic schwannoma, and all cases were treated via complete surgical excision, and for malignant tumors, additional therapy was utilized. All but four cases achieved full remission by final follow-up. Recurrence rate for benign lip schwannomas was 5.3%, which is remarkably different from the standard recurrence rate of 8–24% for benign peripheral schwannomas. Additionally, the proportion of malignant tumors was greater for lip schwannomas than other schwannomas. Lip schwannomas demonstrate different characteristics than schwannomas from other locations on the body, and these remarkable differences highlight significant implications for clinical practice. Complete excision is the primary mode of treatment with overall excellent postoperative prognosis and rare instances of recurrence. Given the rarity of this tumor, this review of available cases serves to comprehensively describe clinical presentation and surgical treatment approaches to upper and lower lip schwannomas.

Impact of climate change on dermatological conditions related to flooding: update from the International Society of Dermatology Climate Change Committee

Abstract

Climate change contributes to the increase in severity and frequency of flooding, which is the most frequent and deadly disaster worldwide. Flood-related damage can be very severe and include health effects. Among those health impacts, dermatological diseases are one of the most frequently encountered. Both infectious and noninfectious dermatological conditions are increasing after flooding. We searched PubMed using the search term climate change OR global warming OR rainfall OR flooding OR skin. Articles published in the English-language literature were included. We also searched the International Society of Dermatology website library on climate change for additional articles. There is an increased risk of trauma during the course of a natural disaster. The majority of post-tsunami wound infections were polymicrobial, but gram-negative bacteria were the leading causes. Infectious diseases with dermatological manifestations, such as impetigo, leptospirosis, measles, dengue fever, tinea corporis, malaria, and leishmaniasis, are important causes of morbidity among flood-afflicted individuals. Insect bites and stings, and parasite infestations such as scabies and cutaneous larva migrans are also frequently observed. Inflammatory conditions including irritant contact dermatitis are among the leading dermatological conditions. Dermatological conditions such as alopecia areata, vitiligo, psoriasis, and urticaria can be induced or exacerbated by psychological conditions post disaster. Prevention is essential in the management of skin diseases because of flooding. Avoiding exposure to contaminated environments, wearing protective devices, rapid provision of clean water and sanitation facilities, prompt vector controls, and education about disease risk and prevention are important.

Pathogenesis and treatment options for chemotherapy-induced alopecia: a systematic review

Abstract

Chemotherapy-induced alopecia (CIA) is one of the most troubling long-lasting side effects of cancer treatment. An estimated 65% of patients undergoing classic chemotherapy will experience hair loss, which is an extremely upsetting adverse event for many. CIA has been traditionally considered to be a diffuse, nonscarring alopecia; however, there are increasing reports of permanent hair loss post chemotherapy. Despite its large impact on patients, there are few proven treatments for CIA. Recent advancements in understanding the pathogenesis of hair loss are promising novel preventative and therapeutic strategies. Currently, scalp cooling during chemotherapy is the most effective preventive intervention with response rates ranging from 50 to 80%. To avoid patient morbidity, clinicians should be aware of the pathogenesis of CIA, characteristic patterns of hair loss associated with specific drug regimens, preventive measures that may be taken, and therapeutic options post chemotherapy. The following represents an updated systematic review of CIA, including characteristic clinical patterns, pathophysiology of the disease, therapeutic approaches, as well as a cost-effective analysis to assess the significance of this toxicity.

Incidence of diseases primarily affecting the skin by age group: population-based epidemiologic study in Olmsted County, Minnesota, and comparison with age-specific incidence rates worldwide

Abstract

Understanding the effects of age on the epidemiology of diseases primarily affecting the skin is important to the practice of dermatology, both for proper allocation of resources and for optimal patient-centered care. To fully appreciate the effect that age may have on the population-based calculations of incidence of diseases primarily affecting the skin in Olmsted County, Minnesota, and worldwide, we performed a review of all relevant Rochester Epidemiology Project–published data and compared them to similar reports in the worldwide English literature. Using the Rochester Epidemiology Project, population-based epidemiologic studies have been performed to estimate the incidence of specific skin diseases over the past 50 years. In older persons (>65 years), nonmelanoma skin cancer, lentigo maligna, herpes zoster, delusional infestation, venous stasis syndrome, venous ulcer, and burning mouth syndrome were more commonly diagnosed. In those younger than 65 years, atypical nevi, psoriatic arthritis, pityriasis rosea, herpes progenitalis, genital warts, alopecia areata, hidradenitis suppurativa, infantile hemangioma, Behçet's disease, and sarcoidosis (isolated cutaneous, with sarcoidosis-specific cutaneous lesions and with erythema nodosum) had a higher incidence. Many of the incidence rates by age group of diseases primarily affecting the skin derived from the Rochester Epidemiology Project were similar to those reported elsewhere.

Harlequin ichthyosis due to novel splice site mutation in the ABCA12 gene: postnatal to prenatal diagnosis

Abstract

Background

Harlequin ichthyosis (HI) is a severe genetic disorder caused by the mutation in the ABCA12 gene. Infants born with this condition have markedly thickened, hard stratum corneum skin all over the body.

Methods

A female child born with a thick white plate of skin with deep cracks all over the body was investigated for genes associated with congenital Ichthyosis by Next Generation sequencing. The variant relevant to the clinical indications was identified using Picard and GATK version 3.6. Variant's pathogenicity was predicted by "in silico" tools like Mutation Taster 2, Mutation Assessor and LRT. Bidirectional Sanger sequencing further validated the same variant detected in the proband and confirmed in the parental blood and CVS.

Results

A homozygous 5′ splice site variation that affects the position at 4 nucleotides downstream to the donor proximal splice site of intron 40 (c.5939+4A>G; ENST00000272895) of the ABCA12 gene was detected in the proband, and the parents were heterozygous for the same variant. This led to the confirmation of diagnosis of Harlequin ichthyosis in the proband. "In silico" prediction of the variant was found to be damaging by MutationTaster2. The CVS sample during subsequent pregnancy was confirmed to be heterozygous for the same variant.

Conclusions

The novel intronic mutation found in the proband confirmed the clinical diagnosis as a severe type of HI and has helped the family in providing precise genetic counseling for further prevention of the disease and carrier screening of other family members.

GAPO syndrome: a rare genodermatosis presenting with unique features

No difference in UVB-induced changes in antigen-presenting cells and in cytokines between subjects with and without loss-of-function mutations in FLG

Abstract

Ultraviolet B (UVB) irradiation-induced skin inflammation leads to epidermal depletion of Langerhans cells (LCs), which is followed by a rapid influx of monocytes.(1) Approximately 10% of Northern Europeans carry loss-of-function mutations in the filaggrin gene (FLG) which cause partial or complete lack of epidermal filaggrin and filaggrin metabolites.(2) Deficit of the filaggrin metabolite trans-urocanic acid has been shown to cause an increased keratinocyte photosensitivity to UVB irradiation in human skin models.(3)

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