Seasonal variation of heavy metals in water, sediment, and highly consumed cultured fish ( Labeo rohita and Labeo bata ) and potential health risk assessment in aquaculture pond of the coal city, Dhanbad (India)

Abstract

The extent of heavy metal pollution and their impact on the various component of urban aquaculture pond (India) were investigated on the basis of seasonal variation. The water, sediment, and fish samples (Labeo rohita and Labeo bata) were collected and analyzed to assess the metal toxicity. In the sediment, geoaccumulation index (I_geo), contamination factor (CF), pollution load index (PLI), and ecological risk index (ERI) were calculated. The estimated daily dietary intake (EDI) for As, Cd, Cr, Mn, Pb, and Zn was estimated in adult and children on the basis an average amount of fish consumed by the Indian people and its associated health hazard with was also assessed in terms of target hazard quotients (THQs). The concentration of metals in all the analyzed samples was found higher during pre-monsoon season. While, in case of fish, L. bata species has higher metal accumulation rate during both the seasons than the L. rohita because of their bottom dweller feeding habit. The order of metals in L. bata muscles is Zn > Mn > Pb > Cr > As > Cd. The I_geo value for Zn (2.66 to 3.68) was found to be highest and followed by Cd (1.65 to 3.52) and Pb (1.52 to 2.55) indicating moderate to highly polluted sediment quality. The values of ERI were significantly high during pre-monsoon period and varied from 319 to 557, representing very high metal contamination. From the human health perspective, present study highlighted that the local inhabitants who rely on this valuable pond for fish consumption are exposed chronically to As and Pb pollution due to higher THQ values, especially from the intake of L. bata.

Metals in Racomitrium lanuginosum from Arctic (SW Spitsbergen, Svalbard archipelago) and alpine (Karkonosze, SW Poland) tundra

Abstract

Arctic-alpine tundra habitats are very vulnerable to the input of relatively small amounts of xenobiotics, and thus their level in such areas must be carefully controlled. Therefore, we collected the terrestrial widespread moss Racomitrium lanuginosum (Hedw.) Brid. in Spitsbergen in the Arctic moss lichen tundra and, for comparison, in the Arctic-alpine tundra in the Karkonosze (SW Poland). Concentrations of the elements Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Na, Ni, Pb, V, and Zn in this species and in the parent rock material were measured. We tested the following hypothesis: R. lanuginosum from Spitsbergen contains lower metal levels than the species from the Karkonosze collected at altitudes influenced by long-range transport from former Black Triangle industry. Principal component and classification analysis (PCCA) ordination revealed that mosses of Spitsbergen were distinguished by a significantly higher Na concentration of marine spray origin and mosses of Karkonosze were distinguished by significantly higher concentrations of Cd, Cr, Cu, Fe, Hg, Li, Mn, Pb, V, and Zn probably from long-range atmospheric transport. The influence of the polar station with a waste incinerator resulted in significantly higher Co, Li, and Ni concentrations in neighbouring mosses in comparison with this species from other sites. This investigation contributes to the use of R. lanuginosum as a bioindicator for metal contamination in Arctic and alpine tundra regions characterised by severe climate habitats with a restricted number of species. This moss enables the control of pollution usually brought solely by long-range atmospheric transport in high mountains as well as in Arctic areas.

Comparison of emerging contaminants in receiving waters downstream of a conventional wastewater treatment plant and a forest-water reuse system

Abstract

Forest-water reuse (FWR) systems treat municipal, industrial, and agricultural wastewaters via land application to forest soils. Previous studies have shown that both large-scale conventional wastewater treatment plants (WWTPs) and FWR systems do not completely remove many contaminants of emerging concern (CECs) before release of treated wastewater. To better characterize CECs and potential for increased implementation of FWR systems, FWR systems need to be directly compared to conventional WWTPs. In this study, both a quantitative, targeted analysis and a nontargeted analysis were utilized to better understand how CECs release to waterways from an FWR system compared to a conventional treatment system. Quantitatively, greater concentrations and total mass load of CECs was exhibited downstream of the conventional WWTP compared to the FWR. Average summed concentrations of 33 targeted CECs downstream of the conventional system were ~ 1000 ng/L and downstream of the FWR were ~ 30 ng/L. From a nontargeted chemical standpoint, more tentatively identified chemicals were present, and at a greater relative abundance, downstream of the conventional system as well. Frequently occurring contaminants included phthalates, pharmaceuticals, and industrial chemicals. These data indicate that FWR systems represent a sustainable wastewater treatment alternative and that emerging contaminant release to waterways was lower at a FWR system than a conventional WWTP.

Cathepsin D contributes to the accumulation of advanced glycation end products during photoaging

Advanced glycation end products (AGEs) are the final products of nonenzymatic glycation of reducing sugars and reactive aldehydes with proteins, lipids and nucleic acids [1]. As AGEs alter the structure and function of proteins, they contribute to the pathogenesis of many diseases, especially diabetes and aging [2]. Skin is the largest organ of human body, and one typical feature of its aging is the accumulation of AGEs [3]. Glycation-associated skin autofluorescence has been found to be correlated with chronological aging in a large number of healthy subjects [4,5].

MITF-M Regulates Melanogenesis in Mouse Melanocytes

The microphthalamia-associated transcription factor (Mitf) gene was first found in descendants of an irradiated male mouse in the 1940s [1]. Using a transgenic insertional mutations at the Mitf locus, the Mitf gene was first cloned by Arnheiter and his colleagues in 1993 [2]. The Mitf gene is conserved in various vertebrate species, including human, rat, mouse, hamster, chicken and quail [3]. Mitf is known to be essential for melanin-bearing pigment cells across species and tissue types. It encodes basic-helix-loop-helix leucine zipper proteins, which are able to form DNA-binding heterodimers with highly homology-related factors.

Home-based contact immunotherapy with diphenylcyclopropenone for alopecia areata is as effective and safe as clinic-based treatment in patients with stable disease: A retrospective study of 40 patients

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Solam Lee, Won-Soo Lee

Crowdsourcing dermatology: DataDerm, big data analytics, and machine learning technology

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Andrew J. Park, Justin M. Ko, Robert A. Swerlick

Table of Contents

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Forehead horizontal primary closure: A retrospective analysis of 25 cases assessing for long-term eyebrow asymmetry

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Logan M. Skelley, Daniel S. Winchester, Randall K. Roenigk

Information for Readers

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

JAAD Case Reports Article List

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Satisfaction with care and likelihood to recommend ratings attributed to dermatology trainees

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Laura E. McDermott, Margaretta Midura, Vassiliki Papagermanos, Joslyn Kirby, Karolyn A. Wanat, Leah T. Belazarian, Cory Dunnick, Jessica S. Mounessa, Stephanie A. Savory, Nidhi Avashia-Khemka, Andrew Strunk, Amit Garg

Journal Based CME Instructions and Information

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Maintenance of Certification: A grandfatherly ethical analysis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Benjamin K. Stoff, Lionel Bercovitch, Jane M. Grant-Kels

Editorial Board

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship with rosacea

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Cristina Pindado-Ortega, David Saceda-Corralo, Diego Buendía-Castaño, Pablo Fernández-González, Óscar M. Monero-Arrones, Pablo Fonda-Pascual, Ana R. Rodrigues-Barata, Pedro Jaén-Olasolo, Sergio Vañó-Galván

Answers to CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Comparison of cyclic and continuous 308-nm excimer laser treatments for vitiligo: A randomized controlled noninferiority trial

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Jae Min Sung, Jung Min Bae, Hee Young Kang

Weight change and risk of onychomycosis: A nationwide cohort study in Korea

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Seong Jun Ha, Kyung Do Han, Yumee Song, Ji Hyun Lee

CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Risk of melanoma in patients with multiple myeloma: A Surveillance, Epidemiology, and End Results population-based study

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Timothy W. Chang, Amy L. Weaver, Jerry D. Brewer, Robert A. Kyle, Christian L. Baum

Answers to CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

The ethics of medical marijuana in dermatology

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Walter Liszewski, Benjamin K. Stoff, Ronda S. Farah

Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Kelly G. Paulson, Song Youn Park, Natalie A. Vandeven, Kristina Lachance, Hannah Thomas, Aude G. Chapuis, Kelly L. Harms, John A. Thompson, Shailender Bhatia, Andreas Stang, Paul Nghiem
BackgroundMerkel cell carcinoma (MCC) incidence rates are rising and strongly age-associated, relevant for an aging population.ObjectiveDetermine MCC incidence in the United States and project incident cases through the year 2025.MethodsRegistry data were obtained from the SEER-18 Database, containing 6600 MCC cases. Age- and sex-adjusted projections were generated using US census data.ResultsDuring 2000-2013, the number of reported solid cancer cases increased 15%, melanoma cases increased 57%, and MCC cases increased 95%. In 2013, the MCC incidence rate was 0.7 cases/100,000 person-years in the United States, corresponding to 2488 cases/year. MCC incidence increased exponentially with age, from 0.1 to 1.0 to 9.8 (per 100,000 person-years) among age groups 40-44 years, 60-64 years, and ≥85 years, respectively. Due to aging of the Baby Boomer generation, US MCC incident cases are predicted to climb to 2835 cases/year in 2020 and 3284 cases/year in 2025.LimitationsWe assumed that the age-adjusted incidence rate would stabilize, and thus, the number of incident cases we projected might be an underestimate.ConclusionAn aging population is driving brisk increases in the number of new MCC cases in the United States. This growing impact combined with the rapidly evolving therapeutic landscape warrants expanded awareness of MCC diagnosis and management.

Fluorescence quenching of MoS 2 nanosheets/DNA/silicon dot nanoassembly: effective and rapid detection of Hg 2+ ions in aqueous solution

Abstract

Mercury (Hg) contamination of aquatic sites represents a serious risk for human health and the environment. Therefore, effective and rapid monitoring of Hg in aqueous samples is a challenge of timely importance nowadays. In the present study, a rapid and sensitive mercury sensor based on the fluorescence quenching of MoS₂ nanosheets/DNA/silicon dot nanoassembly has been developed for the efficient detection of mercury(II) in aquatic environments. In this process, silicon dots were synthesized through one-step high-temperature calcinations and thermomagnesium reduction method at 900 °C using rice husk as a silicon source, which demonstrates superior photophysical properties and excitation-dependent fluorescence behavior. The interaction between MoS₂ nanosheets/DNA/silicon dot nanoassembly and Hg²⁺ ions was studied using photoluminescence spectroscopy. The addition of Hg²⁺ ions to the assay solution induced the detachment of fluorescent probe from the surface of MoS₂ nanosheets. Thus, the fluorescent probes sustained its fluorescence intensity. The developed sensor was tested on various concentrations of Hg²⁺ ions ranging from 0 to 1000 nM as well as on various metal ions. In addition, MoS₂ nanosheets/DNA/silicon dot nanoassembly fluorescent Hg sensor efficiently detected the presence of Hg²⁺ ions in real-time water samples, which was comparably detected by the conventional atomic absorbance spectrometer (AAS). Overall, our results highlighted the high reliability of the present approach for environmental monitoring of Hg²⁺ ions, if compared to that of the customary method with a lowest detection limit of 0.86 nM.

Larvicidal activity of selected plant extracts and their combination against the mosquito vectors Culex quinquefasciatus and Aedes aegypti

Abstract

In order to develop an environment-friendly botanical mosquito larvicide alternative to the chemical larvicides, extracts were made from the leaves of Hyptis suaveolens, Lantana camara, Nerium oleander, and Tecoma stans with three organic solvents such as methanol (ME), chloroform (CH), and petroleum ether (PE) using a Soxhlet extractor. The plant extracts were screened for larvicidal activity individually and in combination against the larvae of Aedes aegypti and Culex quinquefasciatus as per WHO protocol. Among the extracts, the maximum larvicidal activity was shown by the PE extract of L. camara (LC₅₀ 10.63 mg/L) followed by the PE extract of T. stans (LC₅₀ 19.26 mg/L), ME extract of N. oleander (LC₅₀ 35.82 mg/L), and PE extract of H. suaveolens (LC₅₀ 38.39 mg/L) against Cx. quinquefasciatus. In the case of Ae. aegypti, the PE extract of T. stans showed maximum activity with LC₅₀ value of 55.41 mg/L followed by H. suaveolens (LC₅₀ 64.49 mg/L), PE extract of L. camara (LC₅₀ 74.93 mg/L), and ME extract of N. oleander (LC₅₀ 84.09). A blend of these four extracts resulted in a combination with corresponding LC₅₀ values of 4.32 and 7.19 mg/L against Cx. quinquefasciatus and Ae. aegypti. The predator safety factors were 12.55 and 20.88 for Gambusia affinis with respect to Aedes and Culex larvae for the extract combination. Chemical constituents in extracts were also identified by FT-IR and GC-MS data. The present investigations suggest the possible use of this blend of botanical extracts as an ideal ecofriendly, larvicide against Ae. aegypti and Cx. quinquefasciatus larvae.

Improving photoelectrochemical reduction of Cr(VI) ions by building α-Fe 2 O 3 /TiO 2 electrode

Abstract

Photoelectrochemical process is an environmentally friendly technology and has a wide application in the control of environmental pollutants. Efficient nanophotocatalysts responsive to visible light are still highly attractive. In this work, α-Fe₂O₃/TiO₂ were grown on fluorine doped tin oxide (FTO) substrates by hydrothermal method for photoelectrochemical reduction of Cr(VI). Compared with the separate α-Fe₂O₃ and TiO₂ electrodes, the composite α-Fe₂O₃/TiO₂ electrodes show higher photocurrent density. Under visible light irradiation, 100% removal efficiency of Cr(VI) was obtained after 40 min treatment. The composite α-Fe₂O₃/TiO₂ electrodes showed an enhanced absorbance in visible light region and had good stability to photoelectrochemical reduction of Cr(VI). The role of hole scavengers (citric acid and oxalic acid) and pH values was systematically investigated. This novel intensification approach provides new insight on the application of photoelectrochemical reduction in environmental remediation.

Mediative mechanism of bicarbonate on anaerobic propionate degradation revealed by microbial community and thermodynamics

Abstract

Syntrophic acetogenesis of volatile fatty acids (VFAs) such as propionate and butyrate is considered as the rate-limiting step of anaerobic digestion. Though being extensively researched, the mechanism is not well understood as the main constraint on developing effective solutions to the practical problem. In the present research work, the mediation of methanogenic propionate degradation by exogenous bicarbonate was evaluated, while the mechanism was revealed by microbial community and thermodynamics. It was found that the exogenous bicarbonate not more than 0.10 mol/L acted as a mediative role to enrich syntrophic acetogenic bacteria and decrease the actual Gibbs free energy change (ΔG) of syntrophic acetogenesis reaction, resulted in the increased degradation rate and methane production rate of propionate. The remarkably increased ΔG of methanogenic propionate degradation by the exogenous bicarbonate more than 0.15 mol/L decreased the degradation rate and methane production rate of propionate, though the ΔG of syntrophic acetogenesis reaction was also decreased by the exogenous bicarbonate. This research work provided a control strategy to enhance syntrophic acetogenesis, as well as the methanogenic VFAs degradation.

Role of soil physicochemical properties in quantifying the fate of diuron, hexazinone, and metribuzin

Abstract

The physicochemical properties of soil are fundamental to quantification of the fate of herbicides. Thus, the aim of this research was to evaluate the fate of diuron, hexazinone, and metribuzin in five soils (Clay-1, Clay-2, Loam-1, Loam-2, and Sand), presenting variation in clay content, cation exchange capacity (CEC), pH, and organic carbon (OC). Herbicides radiolabeled with ¹⁴C were applied, and the ¹⁴C–CO₂ released from mineralization was trapped in 0.2 mol L⁻¹ sodium hydroxide solution. The degradation ratio, as well as herbicide-bound residues (non-extractable), transformation products, and residues extractable from soil, was also evaluated. Average ¹⁴C–CO₂ evolution accumulated for diuron mineralization was higher (22.24%) than hexazinone (7.73%) and metribuzin (3.20%). The degradation time half-life (DT50) values for hexazinone correlated with soil OC content. Although no correlation between soil properties and DT50 values was found for metribuzin, the degradation rate and total degree of mineralization were low in sand soil for metribuzin. Regarding diuron, OC content and CEC value appear to be related to mineralization and degradation rate, respectively. Differences in soil properties can influence the persistence and fate of herbicides, affecting their impact on the environment, weed control, and possible effects on subsequent crops.

Rhizospheric effects on atrazine speciation and degradation in laterite soils of Pennisetum alopecuroides (L.) Spreng

Abstract

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a worldwide-used herbicide and often detected in agricultural soils and groundwater at concentrations above the permitted limit, because of its high mobility, persistence, and massive application. This study applied pot experiments to investigate the atrazine contents and speciation during the phytoremediation process by Pennisetum alopecuroides (L.) Spreng. in laterite soils. From the change of the total atrazine and bioavailable atrazine measured by diffusive gradients in thin film (DGT), P. alopecuroides significantly improved atrazine degradation efficiency from 15.22 to 51.46%, attributing to the increasing bioavailable atrazine in rhizosphere. Only a small amount of atrazine was taken up by P. alopecuroides root and the acropetal translocation from roots to shoots was limited. The atrazine speciation was significantly different between rhizosphere and non-rhizosphere, attributing to the declining pH and organic matters in rhizosphere. The relationship between pH and soil-bound/humus-fixed atrazine illustrated the pH-dependant release of the atrazine from soils and the competition between humus adsorption and uptake by P. alopecuroides. The present study reveals the important roles of soil pH and organic matters in atrazine speciation and availability in laterite soils, and provides new insights in the rhizospheric effects on effective phytoremediation of atrazine.

Effect of spent mushroom substrate as a bulking agent on gaseous emissions and compost quality during pig manure composting

Abstract

The aim of this study was to investigate the gaseous emissions (CH₄, N₂O, and NH₃) and compost quality during the pig manure composting by adding spent mushroom substrate (SMS) as a bulking agent. The control treatment was also studied using corn stalk (CS) as a bulking agent. The experiment was conducted in a pilot scale composting reactor under aerobic condition with the initial C/N ratio of 20. Results showed that bulking agents significantly affected gaseous emissions and compost quality. Using SMS as a bulking agent improved composting efficiency by shortening the time for maturity. SMS increased germination index and humic acid of the final compost (by 13.44 and 41.94%, respectively) compared with CS. Furthermore, composting with SMS as a bulking agent could reduce nitrogen loss, NH₃, and N₂O emissions (by 13.57, 35.56, and 46.48%, respectively) compared with the control. SMS slightly increased CH₄ emission about 1.1 times of the CS. However, a 33.95% decrease in the global warming potential of CH₄ and N₂O was obtained by adding SMS treatment. These results indicate that SMS is a favorable bulking agent for reducing gaseous emissions and increasing compost quality.

Revisiting energy intensity convergence: new evidence from OECD countries

Abstract

In this study, we examine the energy intensity convergence in OECD countries within the context of recent developments in unit root analysis by paying attention to modeling structural shifts. We collect the total primary energy consumption/GDP data of 27 OECD countries during the period 1980–2014. The findings indicate that controlling for shifts plays a crucial role, and different approximations in modeling breaks lead to changes in inferences. In conclusion, we present some policy proposals.

Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin Diabetic Wounds Following Combined Red and Infrared Photobiomodulation Treatments

Abstract

Diabetic wounds are a major cause of morbidity among patients with poorly controlled blood glucose levels. Conventional empirical wound care strategies have shown limited efficacy and there is an urgent need to develop novel therapeutic strategies. Photobiomodulation treatments have shown a positive therapeutic effects in several cell culture and animal models. In this study, we examined wound healing in diabetic rats following treatments with two laser wavelengths, namely red (660nm) and infrared (808nm) individually and in combination as compared to routine wound dressings. Immunostaining for TGF-β expression was performed at various times post-wounding. We noted that the combination of red and infrared laser treatments correlated with decreased TGF-β1 levels at late stages in healing. There was no statistical significance with any treatments at an earlier time point. This study emphasizes the role of appropriate laser treatment protocols in modulating wound healing and remodeling responses.

This article is protected by copyright. All rights reserved.

hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human macrophages by Fas down regulation

Abstract

Tuberculosis continues to be one of the deadliest infectious disease worldwide. MicroRNAs (miRNAs) are small non-coding entities that play critical role as post-transcriptional regulators and are transcriptionally deregulated upon mycobacterial infection. In this study, we found significant upregulation of hsa-let-7b-5p in Mycobacterium tuberculosis (MTB) infected THP-1 human macrophages. Concomitantly, we detected the reduced level of Fas protein, one of the targets of hsa-let-7b-5p, in MTB infected THP-1 macrophages. Using luciferase assay a direct interaction between hsa-let-7b-5p and the Fas 3'-untranslated region (UTR) was established. Inhibition of hsa-let-7b-5p augmented the apoptosis of THP-1 cells enabling enhanced clearance of MTB. Our findings suggest that hsa-let-7b-5p helps intracellular survival of MTB in THP-1 cells by down-regulating Fas protein level. This highlights hsa-let-7b-5p as a potential therapeutic target for tuberculosis treatment.

Variable response of nirK and nirS containing denitrifier communities to long term pH manipulation and cultivation

Abstract

Denitrification is a key process responsible for the majority of soil nitrous oxide (N₂O) emissions but the influences of pH and cultivation on the soil denitrifier community remain poorly understood. We hypothesised that the abundance and community structure of the total bacterial community and bacterial denitrifiers would be pH sensitive and that nirK and nirS containing denitrifiers would differ in their responses to change in pH and cultivation. We investigated the effect of long-term pH adjusted soils (ranging from pH 4.2 to pH 6.6) under different lengths of grass cultivation (one, two and three years of ley grass) on the general bacterial and denitrifier functional communities using 16S rRNA, nirK and nirS genes as markers. Denitrifier abundance increased with pH, and at pH below 4.7 there was a greater loss in nirS abundance per unit drop in pH than soils above this threshold pH. All community structures responded to changes in soil pH whilst cultivation only influenced the community structure of nirK. These differences in denitrifier responses highlight the importance of considering both nirK and nirS gene markers for estimating denitrifier activity. Identifying such thresholds in response of the microbial community to changes in pH is essential to understanding impacts of management or environmental change.

The value of knowing how

Abstract

Know-how has a distinctive, non-instrumental value that a mere reliable ability lacks. Some, including Bengson and Moffett (in: Bengson, Moffett (eds) Knowing how, Oxford University Press, Oxford, pp 161–195, 2011) and Carter and Pritchard (Australas J Philos 93(4):799–816, 2015b) have cited a close relation between knowhow and cognitive achievement, and it is tempting to think that the value of know-how rests in that relation. That's not so, however. The value of know-how lies in its relation to the fundamental value of autonomy.

Beauty, odds, and credence

Abstract

This paper considers fair betting odds for certain bets that might be placed in the situation discussed in the so-called Sleeping Beauty Problem. This paper examines what Thirders, Halfers, and Double Halfers must say about the odds as determined by various decision theoretic approaches and argues that Thirders and Halfers have difficulties formulating plausible and coherent positions concerning the relevant betting odds. Double Halfers do not face this problem and that is an important consideration in favor of Double Halfers.

A Green Method to Determine VUV (185 nm) Fluence Rate Based on Hydrogen Peroxide Production in Aqueous Solution

Abstract

A mini-fluidic vacuum ultraviolet/ultraviolet (VUV/UV) photoreaction system (MVPS) was developed in our previous study. Based on the MVPS, a green method to determine VUV fluence rate has been developed using the production rate of H₂O₂ when water is exposed to 185 nm VUV. The H₂O₂ production followed pseudo-zero-order reaction kinetics well over the first 10 min of VUV/UV exposure. This new method was well calibrated with a standard cis-cyclooctene cis-trans photoisomerization actinometer as recommended by the International Union of Pure and Applied Chemistry. The apparent quantum yield for H₂O₂ production by 185 nm VUV irradiation of water was determined to be 0.024 ± 0.002. As the solution pH increased from 5.0 to 8.0, the H₂O₂ production rate decreased from 0.83 to 0.40 μM min^–1. Dissolved oxygen had a negligible influence on the H₂O₂ production. This study proposes a novel VUV fluence rate determination method with advantages of non-toxicity, low detection limits, low costs and convenience, and it can be used as a good alternative to traditional actinometers.

This article is protected by copyright. All rights reserved.

Preconditioning With Low Level Laser Irradiation Enhances the Therapeutic Potential of Human Adipose-derived Stem Cells in a Mouse Model of Photoaged Skin

Abstract

The present study was conducted to explore the therapeutic potential of human adipose-derived stem cells (ADSCs) irradiated with a low level laser (LLL). Cultured ADSCs were treated with 650-nm GaAlAs laser irradiation at 2, 4, and 8 J/cm². Cell proliferation was quantified by MTT assays, cytokine secretion was determined by enzyme-linked immunosorbent assays, and adipogenic differentiation was examined by oil red O staining. Additionally, the expression profiles of putative ADSC surface markers were analyzed by quantitative real-time PCR. In addition, a mouse photoaged skin model was established by UVB irradiation. Effects of GaAlAs-laser-treated ADSCs on thicknesses of the epidermis and dermis were analyzed by hematoxylin and eosin staining. The results showed that GaAlAs laser treatment of cells at a radiant exposure of 4 J/cm² enhanced ADSC proliferation and adipogenic differentiation, and increased secretion of growth factors. Furthermore, GaAlAs laser irradiation upregulated the expression of putative ADSC surface markers. In the mouse model of photoaged skin, ADSCs treated with GaAlAs laser irradiation had a markedly decreased the epidermal thickness and increased dermal thickness of photoaged mouse skin. Our data indicate that LLL irradiation is an effective biostimulator of ADSCs and might enhance the therapeutic potential of ADSCs for clinical use.

This article is protected by copyright. All rights reserved.

Human papillomavirus infection and lichen sclerosus: coincidence or link?

When trichoscopy enlightens clinics: more about discoid lupus

Composition as pattern

Abstract

I argue for patternism, a new answer to the question of when some objects compose a whole. None of the standard principles of composition comfortably capture our natural judgments, such as that my cat exists and my table exists, but there is nothing wholly composed of them. Patternism holds, very roughly, that some things compose a whole whenever together they form a "real pattern". Plausibly we are inclined to acknowledge the existence of my cat and my table but not of their fusion, because the first two have a kind of internal organizational coherence that their putative fusion lacks. Kolmogorov complexity theory supplies the needed rigorous sense of "internal organizational coherence".

Ecological and human health risks arising from exposure to metals in urban soils under different land use in Nigeria

Abstract

The concentrations of eight metals (Cd, Pb, Cr, Ni, Cu, Mn, Zn and Fe) were measured in soils under different land use in an urban environment of the Niger Delta in Nigeria. The aim was to provide information on the potential ecological and human health risks associated with human exposure to metals in these soils. The potential ecological risk due to metals in soils of these land use types falls in the range of low to moderate ecological risk with a significant contribution from Cd. The severity of the individual metals to ecological risk in these land use types followed the order Cd > Pb > Zn > Cu > Ni > Cr > Mn. The non-carcinogenic risk, expressed in terms of the hazard index (HI), arising through exposure to metals through oral, dermal and inhalation pathways, was greater than 1 for children in the majority of the land use types and less than 1 for adults for all land use types. This indicated that there are considerable non-cancer risks arising from childhood exposure to metals in soils of these land use types. The cancer risk values were within acceptable threshold values indicating a negligible cancer risk for both children and adults exposed to metals in these urban soils.

Impact of hand eczema on quality of life: metropolitan versus non-metropolitan areas

Summary

Background

An inverse relationship between disease severity and health-related quality of life (HR-QoL) in patients with hand eczema is well established, but modifying effects of demographic variables have been less well studied.

Objective

To identify the influence of metropolitan versus non-metropolitan residence on the relationship between disease severity and HR-QoL in patients with occupational hand eczema.

Methods

The city of Copenhagen and the rest of Zealand were defined as metropolitan and non-metropolitan areas, respectively. Participants were 773 persons with occupational hand eczema. A questionnaire on the severity of hand eczema and HR-QoL was sent to all participants.

Results

The odds for reporting moderate to high severity of occupational hand eczema were significantly lower in the metropolitan population than in the non-metropolitan population [odds ratio (OR): 0.42; 95%CI: 0.23–0.75], whereas low dermatology-related quality of life was more prevalent in metropolitan than in non-metropolitan patients (OR: 1.31; 95%CI: 0.83–2.05), indicating that hand eczema had a more pronounced negative effect in metropolitan patients, in spite of less severe eczema.

Conclusion

Our data indicate that area of residence has a modifying effect on the relationship between disease severity and HR-QoL, with a more negative impact on HR-QoL in metropolitan than in non-metropolitan areas. This information is important with respect to fully appreciating the burden of occupational hand eczema.

The CBTRUS story: providing accurate population-based statistics on brain and other central nervous system tumors for everyone

The Central Brain Tumor Registry of the United States (CBTRUS) was established to provide descriptive statistical data on all primary brain tumors. The following editorial describes some of the historical events that led to its establishment and its current role as the recognized "go-to" resource for researchers; clinicians and treatment facilities; federal and state agencies; manufacturers of medical drugs and devices; and organizations that provide education, emotional support, and guidance for brain tumor patients and their caregivers.

Highlights from the Literature

Corrigendum

Corrigendum to Beier et al. Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro Oncol (doi: https://doi.org/10.1093/neuonc/nox155) first published online 21 August 2017

Forthcoming Meetings

Simultaneous care in neuro-oncology

See the article by Philip et al on pp. 391–399.

A new practical and versatile mouse model of proneural glioblastoma

See the article by Rahme et al. on pp. 332–342.

Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels

Abstract

Despite biological rationale and significant clinical study, the pursuit of small-molecule kinase inhibitors for the treatment of brain cancers has had very limited success. This Advance-in-Brief discusses the need for drugs to achieve free brain penetration to engage their targets where CNS tumors reside. This need to achieve free, as opposed to total, drug concentrations in the brain may be a contributing factor to why so many small-molecule kinase inhibitors have not realized success in the neuro-oncology setting. For kinase targets of interest for brain cancer, either the vast majority of small-molecule inhibitors have data suggesting that free brain penetration would be limited or there are inadequate data to suggest that free brain penetration could be expected. Therefore, kinase targets of interest in the treatment of brain cancers may be inadequately assessed due to a lack of freely brain-penetrant inhibitors available for clinical study. Encouraging recent drug discovery efforts that focused on achieving free brain penetration for cancers in the CNS are highlighted. Still, further efforts are needed to enable thorough clinical evaluation of biological hypotheses.

Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naïve gliomas

Abstract

Background

Few data exist regarding the prognostic value of L-[S-methyl-¹¹C]methionine (MET) PET for treatment-naïve gliomas.

Methods

A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18–84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1–R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan–Meier estimates and the Cox proportional hazards model.

Results

Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57).

Conclusion

This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients.

Metabolic heterogeneity and plasticity of glioma stem cells in a mouse glioblastoma model

Abstract

Background

Glioblastomas have been shown to rely on glycolysis as an energy source. However, recent evidence suggests that at least a subset of glioma cells with stem cell–like properties can thrive on oxidative phosphorylation. It remains unclear whether both metabolic phenotypes support tumor propagation, if they are independent, and how stable they are. The present study investigated these questions with the use of isogenic murine glioma stem cells (GSCs).

Methods

GSCs were established from tumors formed by Ink4a/Arf–null, H-Ras^V12-expressing glioma-initiating cells that differed in extracellular acidification potential. Metabolic characteristics of GSCs were determined by measurement of glucose, oxygen, and glutamine uptake, ATP content, and lactate production. Effects of metabolic inhibitors and changes in oxygen or nutrient availability on lactate production and tumorsphere growth were also determined.

Results

GSCs were found either to consume more glucose and produce more lactate or to consume more oxygen and maintain a higher ATP content depending on the metabolic characteristics of the tumor cells of origin. The latter, mitochondrial-type GSCs increased lactate production after treatment with the oxidative phosphorylation inhibitor oligomycin or phenformin. Exposure to hypoxia also increased lactate production and expression of glycolysis-related enzymes and metabolites in mitochondrial-type GSCs in a reversible manner.

Conclusions

Both glycolytic and mitochondrial-type energy production can sustain tumor propagation by isogenic GSCs. Whereas both phenotypes can be independent and stable, cells that rely on oxidative phosphorylation can also switch to a more glycolytic phenotype in response to metabolic stress, suggesting that plasticity is a further characteristic of GSC metabolism.

Long-term exposure to ambient air pollution and incidence of brain tumor: the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Abstract

Background

Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.

Methods

In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM_2.5, PM₁₀, and PM_coarse), PM_2.5 absorbance, nitrogen oxides (NO₂ and NO_x) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.

Results

Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM_2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10^–5/m³), and weak positive or null associations with the other pollutants. Hazard ratio for PM_2.5 absorbance (1.01; 0.38–2.71 per 10^–5/m³) and all other pollutants were lower for nonmalignant than for malignant brain tumors.

Conclusion

We found suggestive evidence of an association between long-term exposure to PM_2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.

Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment

Abstract

Background

Microglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing, we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1.

Methods

We used quantitative reverse transcriptase PCR, immunofluorescence stainings, western blot, and flow cytometry to identify the various sources of osteopontin (OPN) expression in human and mouse glioblastoma. We implanted wild type GL261 glioblastoma cells, which do not express significant levels of OPN, into wild type and OPN^−/− mice to investigate the role of microenvironment-derived OPN on glioblastoma progression.

Results

Our data indicate that GAMs are the predominant source of OPN in both human and mouse glioblastoma and express only the secreted form of OPN. Loss of microenvironment-derived OPN enhanced tumor progression. Staining by Ki67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling showed no difference in overall cell proliferation but a decreased apoptosis rate in tumors in OPN^−/− mice. CD31 staining showed a significantly decreased number of microvessels in tumors in OPN^−/− mice, accompanied by reduced coverage of vessels with platelet derived growth factor receptor β⁺ pericytes. Flow cytometry analysis revealed a significant increase of CD11b⁺/CD45^low microglia but not of CD11b⁺/CD45^high macrophages/monocytes in tumors in OPN^−/− mice. Sorted CD11b⁺ cells from wild type and OPN^−/− naïve brains and tumors did not show a significant difference in the expression pattern of activation marker genes.

Conclusion

Our results show that in tested human and mouse glioblastoma samples, OPN is predominantly expressed and secreted by GAMs and that, in contrast to OPN expression in the tumor cells per se, loss of stroma-derived OPN creates a glioblastoma-promoting microenvironment.

Molecular differences in IDH wildtype glioblastoma according to MGMT promoter methylation

Abstract

Background

O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma. We investigated whether this marker furthermore defines a molecularly distinct tumor subtype with clinically different outcome.

Methods

We analyzed copy number variation (CNV) and methylation profiles of 1095 primary and 92 progressive isocitrate dehydrogenase wildtype glioblastomas, including paired samples from 49 patients. DNA mutation data from 182 glioblastoma samples of The Cancer Genome Atlas (TCGA) and RNA expression from 107 TCGA and 55 Chinese Glioma Genome Atlas samples were analyzed.

Results

Among untreated glioblastomas, MGMT promoter methylated (mMGMT) and unmethylated (uMGMT) tumors did not show different CNV or specific gene mutations, but a higher mutation count in mMGMT tumors. We identified 3 methylation clusters. Cluster 1 showed the highest average methylation and was enriched for mMGMT tumors. Seventeen genes including gastrulation brain homeobox 2 (GBX2) were found to be hypermethylated and downregulated on the mRNA level in mMGMT tumors. In progressive glioblastomas, platelet derived growth factor receptor alpha (PDGFRA) and GLI2 amplifications were enriched in mMGMT tumors. Methylated MGMT tumors gain PDGFRA amplification of PDGFRA, whereas uMGMT tumors with amplified PDGFRA frequently lose this amplification upon progression. Glioblastoma patients surviving <6 months and with mMGMT harbored less frequent epidermal growth factor receptor (EGFR) amplifications, more frequent TP53 mutations, and a higher tumor necrosis factor–nuclear factor-kappaB (TNF-NFκB) pathway activation compared with patients surviving >12 months.

Conclusions

MGMT promoter methylation status does not define a molecularly distinct glioblastoma subpopulation among untreated tumors. Progressive mMGMT glioblastomas and mMGMT tumors of patients with short survival tend to have more unfavorable molecular profiles.

Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

Abstract

Background

Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy.

Methods

The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy.

Results

Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock.

Conclusions

Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in the treatment of gliomas

Abstract

Background

MicroRNAs (miRs) are promising new therapeutics for glioblastoma. However, which miRs are most effective against glioblastomas and how these miRs should be delivered are major unanswered problems.

Methods

To identify potent antiglioma miRs, we selected 8 miRs based on a literature search and screened them against a panel of glioma stem cell (GSC) lines, representing all of the glioblastoma subtypes defined by The Cancer Genome Atlas. To address delivery, we tested the hypothesis that ex vivo cultured bone marrow–derived mesenchymal stem cells (MSCs) can package miRs into exosomes and that these engineered exosomes can systemically deliver antiglioma miRs to glioblastomas.

Results

Of the screened miRs, we identified miR-124a as the most effective antiglioma agent against GSCs. We then transduced MSCs with lentivirus vectors containing miR-124a and isolated vesicles from the medium. Electron microscopy, western blotting, and Nanosight proved that the isolated vesicles were exosomes. Quantitative PCR documented that these exosomes contained high levels of miR-124a, which was not present in control exosomes. In vitro treatment of GSCs with exosomes containing miR-124a (Exo-miR124) resulted in a significant reduction in viability and clonogenicity of GSCs compared with controls. In vivo treatment of mice harboring intracranial GSC267 with systemically delivered Exo-miR124 resulted in 50% of animals living long term. No evidence of tumor was present on histological analysis of the survivors. Mechanistic studies showed that miR-124a acts by silencing Forkhead box (FOX)A2, resulting in aberrant intracellular lipid accumulation.

Conclusion

MSCs can be used as natural biofactories to produce Exo-miR124, which is an effective antiglioma agent worthy of further clinical evaluation.

A proposed framework of supportive and palliative care for people with high-grade glioma

Abstract

Background

Patients with malignant high-grade glioma (HGG) have significant supportive and palliative care needs, yet few tailored guidelines exist to inform practice. This study sought to develop an HGG framework of supportive and palliative care informed by needs reported by patients, families, and health care professionals (HCPs).

Methods

This study integrates a mixed-methods research program involving: (i) exploring experiences through systematic literature review and qualitative study (10 patients, 23 carers, and 36 HCPs); and (ii) an epidemiological cohort study (N = 1821) describing care of cases of HGG in Victoria, Australia using linked hospital datasets. Recommendations based on these studies were developed by a multidisciplinary advisory committee for a framework of supportive and palliative care based on the findings of (i) and (ii).

Results

Key principles guiding framework development were that care: (i) aligns with patient/family caregiver needs according to illness transition points; (ii) involves continuous monitoring of patient/family caregiver needs; (iii) be proactive in response to anticipated concerns; (iv) includes routine bereavement support; and (v) involves appropriate partnership with patients/families. Framework components and resulting activities designed to address unmet needs were enacted at illness transition points and included coordination, repeated assessment, staged information provision according to the illness transition, proactive responses and referral systems, and specific regular inquiry of patients' and family caregivers' concerns.

Conclusion

This evidence-based, collaborative framework of supportive and palliative care provides an approach for patients with HGG that is responsive, relevant, and sustainable. This conceptual framework requires evaluation in robust clinical trials.

Clinical characteristics associated with postoperative seizure control in adult low-grade gliomas: a systematic review and meta-analysis

Abstract

Background

Epilepsy is the most common symptom in patients with supratentorial low-grade gliomas (LGGs), which adversely affects the patient's quality of life. Poor seizure control with anti-epileptic therapy is an indication for surgery in these patients. Recent studies have sought to identify predictors of postoperative seizure control after surgical resection of LGG; gross total resection was shown to be a significant predictor in this respect. However, the prognostic value of other factors is not clear.

Methods

We performed a systematic review and meta-analysis of 23 studies with a combined study population of 2641 patients with LGG, in order to identify potential factors associated with favorable postoperative seizure control. Data were extracted on age and sex of patient, tumor location, tumor histology, type of seizure, seizure duration, extent of resection, and imaging characteristics.

Results

Patients ≥45 years of age achieved better postoperative seizure control (risk ratio [RR], 0.89; 95% CI, 0.81–0.99). Focal seizures were associated with poor seizure control (RR, 1.32; 95% CI, 1.18–1.49) compared with generalized seizures (RR, 0.77; 95% CI, 0.68–0.87). Prolonged history of seizures (≥1 y) had a negative impact on postoperative seizure control (RR, 1.22; 95% CI, 1.10–1.34). Gross total resection was superior to subtotal resection with respect to postoperative seizure control (RR, 0.68; 95% CI, 0.63–0.73).

Conclusions

This systematic review and meta-analysis identified predictors of postoperative seizure control in patients undergoing surgical resection of LGGs. Our results provide a reference for clinical treatment of LGG-related epilepsy.

A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma

Abstract

Background

Mouse models of glioblastoma (GBM), the most aggressive primary brain tumor, are critical for understanding GBM pathology and can contribute to the preclinical evaluation of therapeutic agents. Platelet-derived growth factor (PDGF) signaling has been implicated in the development and pathogenesis of GBM, specifically the proneural subtype. Although multiple mouse models of PDGF-driven glioma have been described, they require transgenic mice engineered to activate PDGF signaling and/or impair tumor suppressor genes and typically represent lower-grade glioma.

Methods

We designed recombinant lentiviruses expressing both PDGFB and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following stereotactic injection into the dentate gyrus of adult immunocompetent mice. We engineered these viruses to coexpress CreERT2 with PDGFB, allowing for deletion of floxed genes specifically in transduced cells, and designed another version of this recombinant lentivirus in which enhanced green fluorescent protein was coexpressed with PDGFB and CreERT2 to visualize transduced cells.

Results

The dentate gyrus of injected mice showed hypercellularity one week post-injection and subsequently developed bona fide tumors with the pathologic hallmarks of GBM leading to a median survival of 77 days post-injection. Transcriptomic analysis of these tumors revealed a proneural gene expression signature.

Conclusion

Informed by the genetic alterations observed in human GBM, we engineered a novel mouse model of proneural GBM. While reflecting many of the advantages of transgenic mice, this model allows for the facile in vivo testing of gene function in tumor cells and makes possible the rapid production of large numbers of immunocompetent tumor-bearing mice for preclinical testing of therapeutics.

miR miR on the wall, who’s the most malignant medulloblastoma miR of them all?

Abstract

microRNAs (miRNAs) have wide-ranging effects on large-scale gene regulation. As such, they play a vital role in dictating normal development, and their aberrant expression has been implicated in cancer. There has been a large body of research on the role of miRNAs in medulloblastoma, the most common malignant brain tumor of childhood. The identification of the 4 molecular subgroups with distinct biological, genetic, and transcriptional features has revolutionized the field of medulloblastoma research over the past 5 years. Despite this, the growing body of research on miRNAs in medulloblastoma has largely focused on the clinical entity of a single disease rather than the molecular subgroups. This review begins by highlighting the role of miRNAs in development and progresses to explore their myriad of implications in cancer. Medulloblastoma is characterized by increased proliferation, inhibition of apoptosis, and maintenance of stemness programs—features that are inadvertently regulated by altered expression patterns in miRNAs. This review aims to contextualize the large body of work on miRNAs within the framework of medulloblastoma subgroups. The goal of this review is to stimulate new areas of research, including potential therapeutics, within a rapidly growing field.

Title Page

Table of Contents

CME Overview

Dupilumab: A review of its use in the treatment of atopic dermatitis

Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD.

Editorial Board

Atopic Dermatitis in Diverse Racial and Ethnic Groups – Variations in Epidemiology, Genetics, Clinical Presentation, and Treatment

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and black individuals than whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation, and treatment of AD in non-white ethnic groups, which are largely under-appreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non-white patients, as well as greater inclusion of minority groups in clinical trials, in order to develop targeted treatments for a multi-ethnic population.

This article is protected by copyright. All rights reserved.

Gendered Pathways to Burnout: Results from the SALVEO Study

Abstract

Aim

Burnout is a pervasive mental health problem in the workforce, with mounting evidence suggesting ties with occupational and safety outcomes such as work injuries, critical events and musculoskeletal disorders. While environmental [work and non-work, work-to-family conflict (WFC)] and individual (personality) pathways to burnout are well documented, little is known about how gender comes to influence such associative patterns. The aim of the study consisted in examining gendered pathways to burnout.

Methods

Data were derived from the SALVEO study, a cross-sectional study of 2026 workers from 63 workplaces from the province of Québec (Canada). Data were analyzed using multilevel path analysis.

Results

Direct effects of gendered pathways were evidenced for work (e.g. decision latitude) and non-work (e.g. child-related strains) environmental pathways, as well as for individual pathways (i.e. internal locus of control). Indirect effects of gendered pathways were also evidenced, with women reporting higher levels of burnout compared to men due to lower levels of decision latitude and of self-esteem, as well as higher levels of WFC. Women also reported lower burnout levels through investing more time into domestic tasks, which could represent a recovery strategy to highly demanding work. WFC further mediated the associations between working hours and burnout, as well as the between irregular work schedules and burnout. These result suggest than men distinctively reported higher levels of burnout due to the specific nature of their work contract negatively impacting on WFC, and incidentally, on their mental health.

Conclusion

Study results supported our hypotheses positing that gender distinctively shapes environmental and individual pathways to burnout. OHS prevention efforts striving for better mental health outcomes in the workforce could relevantly be informed by a gendered approach to burnout.

Do Women and Men Have the Same Patterns of Multiple Occupational Carcinogenic Exposures? Results from a Cohort of Cancer Patients

Abstract

Complex exposure situations are frequent at the workplace, but few studies have characterized multiple occupational carcinogenic exposures (MOCE) and their gendered differences across jobs' characteristics. We assessed MOCE separately in male and female jobs and identified patterns of MOCE at job level. Participants (834 men and 183 women) were cancer patients recruited between March 2002 and December 2010 in the ongoing SCOP93 cohort study, Seine-Saint-Denis department, France. Job histories were collected through personal interviews, and carcinogenic exposures were assessed by a multidisciplinary expert committee using a list of 53 carcinogens. Proportion of MOCE (i.e. ≥2 carcinogens) was assessed for male and female jobs separately. Principal component analysis combined with hierarchical ascendant classification was used to identify patterns of MOCE. Among the 5202 male jobs and 885 female jobs, respectively 42 and 9% were multi-exposed. Blue-collar workers and jobs in the construction and industry sectors had the highest rates of MOCE, contrasting with jobs held in recent periods (≥1997) and by patients aged ≥45 years at job start. A gradient of MOCE was also observed according to occupational segregation for both men and women. Eight patterns of MOCE were identified among male jobs: widespread carcinogens, mixed silica dust, heavy metals/combustion products, organic compounds/radiation, metal working, solvents/heavy metals, wood dust/formaldehyde/pesticides, and fuel exhausts. Three patterns of MOCE were found among female jobs: biological/organic compounds, industrial working, and fuel exhausts. Some patterns of MOCE were job-specific, whereas other patterns were found across different occupations. These results suggest that patterns of MOCE partly differ between men and women. They stress the importance of gendering multiple exposure assessment studies and point out the inadequacy of occupational disease compensation systems based on a single factor and non-gendered approach of carcinogenesis, ignoring differences between men and women in complex occupational exposure situations.

Health and Work in Women and Men in the Welding and Electrical Trades: How Do They Differ?

Abstract

Objectives

There is little information on how work tasks, demands, and exposures differ between women and men in nominally the same job. This is critical in setting workplace standards that will protect the health of both men and those women moving into less traditional work roles. Information used in setting standards is currently based almost entirely on male workers. This paper describes differences in work and health, and the relation between them, in women and men who have undergone the same trade training for the welding or electrical trades.

Method

Four cohorts were established. Two were women across Canada in the welding and electrical trades who had been in an apprenticeship since 2005. Cohorts of men in the same trades during the same period were established in the province of Alberta, Canada. Participants completed a baseline questionnaire at recruitment and were followed up every 6 months to collect detailed information on work carried out and on their health and habits. At the end of the study (up to 5 years for women and up to 3 years for men), the cohort members completed a final questionnaire including questions on mental health, harassment, and gender.

Results

The four cohorts comprised 1001 welders (447 female; 554 male) and 885 in the electrical trades (438 female; 447 male). Follow-up information was available for 89%. Women were more likely than men to have had some post-secondary education before starting their trade and were less likely to be living as married or to have a child. More welders smoked, and more men were heavy drinkers. At recruitment, more welders than those in the electrical trades reported rhinitis (sneezing and runny nose), depression, and anxiety. Female welders reported more depression (38%) than male welders (30%), compared to 24% in the electrical trades. At first follow-up, new-onset shoulder pain was more frequent in men and new-onset asthma or wheezing in welders. Within each trade, women reported less variety in tasks. Women welders were less likely to be employed in construction than men, and women were less likely to become industrial electricians. Overall, 54% of women and 46% of men reported never using respiratory protection when welding. In the end-of-study questionnaires received to date, 49% reported bullying or harassment during the apprenticeship, with higher proportions in welding than electrical trades and in women compared with men. Such harassment was reflected in higher anxiety and depression scores.

Conclusions:

This is the first report on these four cohorts and demonstrates the capacity for detailed analysis of the differences in exposure and new-onset occupationally related ill-health. While women and men in the same trades appear to be doing broadly similar work, and to have similar patterns on health at the first follow-up, there are some significant differences in the types of employment and variety of tasks. The very detailed information collected will allow more precise estimates of exposures to be correlated with health outcomes at the end of the follow-up period.

Involvement of flexures in an adolescent patient with dermatomyositis: extension of inverse Gottron papules?

Correction to: Removal of fluoroquinolone from aqueous solution using graphene oxide: experimental and computational elucidation

Abstract

Unfortunately, the original version of this article contains a mistake. The figures no. 10, 11, 12 and 13 in the original version of the article should be replaced by the figures shown in this paper.

Handheld reflectance confocal microscopy, dermatoscopy and histopathological correlation of common inflammatory balanitis

Abstract

Background

The term balanitis includes a variety of inflammatory skin diseases involving the glans penis whose clinical diagnosis may be challenging. A biopsy is often required to obtain a definitive diagnosis, although it is barely accepted by patients. Reflectance confocal microscopy (RCM), that provides a real-time, en face imaging of the epidermis and upper dermis, is currently utilized for the diagnosis of some neoplastic and inflammatory skin diseases. The aim of this study was to analyze the RCM handheld findings of some common balanitis and to correlate them with dermatoscopy and histopathological features.

Materials and Methods

Thirty-two patients with biopsy-proven diagnosis of psoriatic balanitis (10 patients), Zoon's balanitis (11 patients) and lichen sclerosus et atrophicus (11 patients) were evaluated using a handheld RCM device and ×10 dermatoscopy.

Results

At the end of the study, each disorder presented specific RCM patterns that correlated with dermatoscopy and histopathological findings.

Conclusion

The use of handheld RCM as complementary tool in everyday clinical practice for the evaluation of inflammatory diseases involving sensitive areas such as male genitalia, may contribute to reduce the need of invasive procedures.

A novel electrocatalytic approach for effective degradation of Rh-B in water using carbon nanotubes and agarose

Abstract

Carbon nanotubes (CNTs)/agarose (AG) membrane on the ITO (indium tin oxide) conductive glass, with high efficiency of electrocatalytic degradation for rhodamine B (Rh-B) in water, was prepared using an easy and green method. The prepared CNTs/AG membrane was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive spectra (EDS), infrared spectroscopy (IR), and electrochemical impedance spectroscopy (EIS). The results revealed that CNTs were dispersed in the AG membrane. Additionally, the electrocatalytic activities for Rh-B were conducted on the electrochemical workstation with a three-electrode system. Both initial pH and potential played an important role in the process of electrocatalytic degradation. At pH 3 and potential reaching 4 V, the removal rate of Rh-B (10 mg/L) in water achieved 96% within 20 min. The stability of the prepared CNTs/AG membrane was also investigated. Besides, the toxicities of the main intermediates from the electrocatalytic degradation for Rh-B were calculated using the ECOSAR program and EPIWIN software, and results indicated that the toxicities of some intermediates were higher than those of the parent pollutant (Rh-B). These findings provided a light-spot to simplify the preparation of efficient working electrode and emphasized the possible potential risks from intermediates at the same time.

Swift fabrication of Ag nanostructures using a colloidal solution of Holostemma ada-kodien (Apocynaceae) – Antibiofilm potential, insecticidal activity against mosquitoes and non-target impact on water bugs

Publication date: Available online 17 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Sami A. Alyahya, Marimuthu Govindarajan, Naiyf S. Alharbi, Shine Kadaikunnan, Jamal M. Khaled, Ramzi A. Mothana, Mohammed N. Al-anbr, Baskaralingam Vaseeharan, Ramachandran Ishwarya, Mariappan Yazhiniprabha, Giovanni Benelli
Recent research in parasitology focused on the efficacy of green fabricated nanomaterials as novel insecticides. In this study, we synthesized poly-dispersed, stable, and cluster-shaped silver nanoparticles (AgNPs) using the leaf extract of Holostemma ada-kodien. The cluster-shaped AgNPs were characterized by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction analysis. The efficacy of H. ada-kodien leaf extract and AgNPs in vector control was evaluated against the mosquitoes Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus, which act as major vectors of important parasitic and arboviral diseases. AgNPs showed higher toxicity if compared to the H. ada-kodien leaf aqueous extract, LC50 towards larvae of A. stephensi, A. aegypti, and C. quinquefasciatus were 12.18, 13.30, and 14.70 μg/ml, respectively. AgNPs tested on non-target water bugs, Diplonychus indicus, LC50 value was 623.48 μg/ml. Furthermore, 100 μl/ml of AgNPs achieved significant antimicrobial activity against Bacillus pumilus, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris, and Candida albicans. Light and confocal laser scanning microscopy highlighted a major impact of the H. ada-kodien-synthesized AgNPs on the external topography and architecture of microbial biofilms for both Gram-positive and Gram-negative bacteria. Overall, this study sheds light on the insecticidal and antibiofilm potential of H. ada-kodien-synthesized AgNPs, a potential green resource for the rapid synthesis of polydispersed, cluster-shaped, and highly stable AgNPs.

Graphical abstract

Editorial Board

The combination of Luffa cylindrical fibers and metal oxides offers a highly performing hybrid fiber material in water decontamination

Abstract

The present investigation aims to prepare a hybrid material from Luffa cylindrica and metal oxides (ZnO, Al₂O₃) by precipitation for different percentages of zinc and aluminum (1, 2, and 4%) with a determined amount of biomass (a diameter of 250 μm). Physicochemical characterization of "Luffa cylindrica" and "Luffa cylindrica-metal oxides" was carried out by Boehm titration, pH_PZC determination, scanning electron microscopy (SEM), and FTIR spectroscopic analysis. The process was optimized according to the adsorbed amount of methylene blue: MB (cationic dye) and methyl orange: MO (anionic dye) onto Luffa cylindrica and hybrid materials prepared. The results demonstrated the efficiency of the designed hybrid materials in removing MB and MO, accelerating the biosorption process and improving the performance of Luffa cylindrica fibers. The highest quantities adsorbed of dyes were obtained by the hybrid material prepared using 4% ZnO. Finally, the Brouers-Sotolongo mathematical modeling of kinetics was used in order to describe the pollutants retention process.

Lethal and sub-lethal effects of cyproconazole on freshwater organisms: a case study with Chironomus riparius and Dugesia tigrina

Abstract

The fungicide cyproconazole (CPZ) inhibits the biosynthesis of ergosterol, an essential sterol component in fungal cell membrane and can also affect non-target organisms by its inhibitory effects on P450 monooxygenases. The predicted environmental concentration of CPZ is up to 49.05 μg/L and 145.89 μg/kg in surface waters and sediments, respectively, and information about CPZ toxicity towards non-target aquatic organisms is still limited. This study aimed to address the lack of ecotoxicological data for CPZ, and thus, an evaluation of the lethal and sub-lethal effects of CPZ was performed using two freshwater invertebrates (the midge Chironomus riparius and the planarian Dugesia tigrina). The estimated CPZ 48 h LC₅₀ (95% CI) was 17.46 mg/L for C. riparius and 47.38 mg/L for D. tigrina. The emergence time (EmT₅₀) of C. riparius was delayed by CPZ exposure from 0.76 mg/L. On the other hand, planarians showed higher tolerance to CPZ exposure. Sub-lethal effects of CPZ on planarians included reductions in locomotion (1.8 mg/L), delayed photoreceptors regeneration (from 0.45 mg/L), and feeding inhibition (5.6 mg/L). Our results confirm the moderate toxicity of CPZ towards aquatic invertebrates but sub-lethal effects observed also suggest potential chronic effects of CPZ with consequences for population dynamics.

Uptake and elimination kinetics of trifluralin and pendimethalin in Pheretima spp. and Eisenia spp.

Abstract

The purpose of this study was to clarify the kinetic bioaccumulation potential of herbicides in the earthworm, Pheretima spp., the most common earthworms throughout Asia, and Eisenia spp., litter-feeding earthworms included in the test species recommended by the Organization for Economic Co-operation and Development. The kinetic bioaccumulation factors of trifluralin and pendimethalin were estimated from an uptake test for 10 or 12 days and from an elimination test for 10 days. The time required to reach a steady state following herbicide exposure was 7 days for both herbicides in Eisenia spp. and 1 day in Pheretima spp. The uptake rate constant (g-soil/g-worm/day) and elimination rate constant (per day) for trifluralin were 2.1 and 0.23 in Eisenia spp. and 0.42 and 0.45 in Pheretima spp., respectively, and those for pendimethalin were 1.5 and 0.26 in Eisenia spp. and 0.27 and 1.0 in Pheretima spp., respectively. Kinetic bioaccumulation factors of both herbicides were relatively close to bioaccumulation factors in steady state and were higher in Eisenia spp. (8.9 for trifluralin and 5.7 for pendimethalin) than in Pheretima spp. (0.95 and 0.26). These results demonstrated that the herbicide bioaccumulation risk is lower for Pheretima spp. than for Eisenia spp. because of the lower uptake rate and higher elimination rate in Pheretima spp.

Soft Ethics and the Governance of the Digital

Serlopitant for the treatment of chronic pruritus: results of a randomized, multicenter, placebo-controlled phase 2 clinical trial

The substance P/neurokinin 1 receptor (NK1R) pathway is critical in chronic pruritus; anecdotal evidence suggests antagonism of this pathway can reduce chronic itch.

Diana and Ernie return: on Carolina Sartorio’s Causation and Free Will

Abstract

In the final chapter of her Causation and Free Will, Carolina Sartorio offers (among other things) a novel reply to an original-design argument for the thesis that determinism is incompatible with free will and moral responsibility, an argument that resembles Alfred Mele's zygote argument in Free Will and Luck. This article assesses the merits of her reply. It is concluded that Sartorio has more work to do if she is to lay this style of argument to rest.

Electrokinetic-Fenton remediation of organochlorine pesticides from historically polluted soil

Abstract

Soil contamination by persistent organic pollutants (POPs) poses a great threat to historically polluted soil worldwide. In this study, soils were characterized, and organochlorine pesticides contained in the soils were identified and quantified. Individual electrokinetic (IE), EK-Fenton-coupled technologies (EF), and enhanced EK-Fenton treatment (E-1, E-2, and E-3) were applied to remediate soils contaminated with hexachloro-cyclohexane soprocide (HCH) and dichloro-diphenyl-trichloroethane (DDT). Variation of pH, electrical conductivity, and electroosmotic flow was evaluated during the EK-Fenton process. The IE treatment showed low removal efficiency for HCHs (30.5%) and DDTs (25.9%). In the EF treatment, the highest removal level (60.9%) was obtained for α-HCH, whereas P,P-DDT was the lowest (40.0%). Low solubility of pollutants impeded the HCH and DDT removal. After enhanced EK-Fenton treatment, final removal of pollutants decreased as follows: β-HCH (82.6%) > γ-HCH (81.6%) > α-HCH (81.2%) > δ-HCH (80.0%) > P,P-DDD (73.8%) > P,P-DDE (73.1%) > P,P-DDT (72.6%) > O,P-DDT (71.5%). The results demonstrate that EK-Fenton is a promising technology for POP removal in historically polluted soil.

Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation model: role of Ape1 function

Abstract

Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression. This increase in mRNA expression is consistent throughout the chronic exposure. Additionally, we also found an impaired function of Ape1 through molecular beacon-based assay. To evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low concentrations of lead before induction of transformation with n-methyl-n-nitrosoguanidine (MNNG) (0.5 μg/mL) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 μg/mL) (a classical two-step protocol). Morphological cell transformation increased in response to lead pretreatment that was paralleled with an increase in Ape1 mRNA and protein overexpression and an impairment of Ape1 activity and correlating with foci number. In addition, we found that lead pretreatment and MNNG (transformation initiator) increased DNA damage, determined by comet assay. Our data suggest that low lead concentrations (5, 30 μM) could play a facilitating role in cellular transformation, probably through the impaired function of housekeeping genes such as Ape1, leading to DNA damage accumulation and chromosomal instability, one of the most important hallmarks of cancer induced by chronic exposures.

Analysing the accuracy of machine learning techniques to develop an integrated influent time series model: case study of a sewage treatment plant, Malaysia

Abstract

The function of a sewage treatment plant is to treat the sewage to acceptable standards before being discharged into the receiving waters. To design and operate such plants, it is necessary to measure and predict the influent flow rate. In this research, the influent flow rate of a sewage treatment plant (STP) was modelled and predicted by autoregressive integrated moving average (ARIMA), nonlinear autoregressive network (NAR) and support vector machine (SVM) regression time series algorithms. To evaluate the models' accuracy, the root mean square error (RMSE) and coefficient of determination (R²) were calculated as initial assessment measures, while relative error (RE), peak flow criterion (PFC) and low flow criterion (LFC) were calculated as final evaluation measures to demonstrate the detailed accuracy of the selected models. An integrated model was developed based on the individual models' prediction ability for low, average and peak flow. An initial assessment of the results showed that the ARIMA model was the least accurate and the NAR model was the most accurate. The RE results also prove that the SVM model's frequency of errors above 10% or below − 10% was greater than the NAR model's. The influent was also forecasted up to 44 weeks ahead by both models. The graphical results indicate that the NAR model made better predictions than the SVM model. The final evaluation of NAR and SVM demonstrated that SVM made better predictions at peak flow and NAR fit well for low and average inflow ranges. The integrated model developed includes the NAR model for low and average influent and the SVM model for peak inflow.

Nerve reinnervation and itch behaviour in a rat burn wound model

ABSTRACT

In this study, we investigated whether post-burn itch in rats, after a full thickness burn, is correlated to the nervous reinnervation of the burn wound area. For this purpose, we determined scratching duration (expressed as sec/hr) at 24 hours, 2, 4, 8 and 12 weeks post-burn and combined this with immunohistochemistry for protein gene product 9.5 (PGP9.5) to identify all nerve fibers, calcitonin gene related peptide (CGRP) to identify peptidergic fibers, tyrosine hydroxylase (TH) for sympathetic fibers and growth-associated protein 43 (GAP-43) for regrowing fibers.

We found a modest, but highly significant, increase in scratching duration of all burn wound rats from 3 to 12 weeks post-burn (maximally 63±9.5 sec/hr compared to sham 3.1±1.4 sec/hr at 9 weeks). At 24 hours post-burn, all nerve fibers had disappeared from the burn area. Around 4 weeks post-burn PGP 9.5- and CGRP-immunoreactive nerve fibers returned to control levels. TH- and GAP-43-IR nerve fibers, which we found to be almost completely co-localized, did not regrow. No correlation was found between scratching duration and nervous reinnervation of the skin.

The present results suggest that in rat, like in human, burn wound healing will induce increased scratching, which is not correlated to nervous reinnervation. This article is protected by copyright. All rights reserved.

Dicer inactivation stimulates limb regeneration ability in Xenopus laevis

Abstract

The ontogenetic decline of regeneration capacity in the anuran amphibian Xenopus makes it an excellent model for regeneration studies. However, the cause of the regeneration ability decline is not fully understood. MicroRNAs regulate animal development, and have been indicated in various regeneration situations. However, little is known about the role of microRNAs during limb regeneration in Xenopus. This study investigates the effect of Dicer, an enzyme responsible for microRNA maturation, on limb development and regeneration in Xenopus. Dicer is expressed in the developing Xenopus limbs, and is upregulated after limb amputation during both regeneration-competent and -deficient stages of tadpole development. Inactivation of Dicer in early (NF stage 53) tadpole limb buds leads to shorter tibulare/fibulare formation, but does not affect limb regeneration. However, in late stage, regeneration-deficient tadpole limbs (NF stage 57), Dicer inactivation restores the regeneration blastema, and stimulates limb regeneration. Thus, our results demonstrated that Xenopus limb regeneration can be stimulated by inactivation of Dicer in non-regenerating tadpoles, indicating that microRNAs present in late stage tadpole limbs may be involved in the ontogenetic decline of limb regeneration in Xenopus. This article is protected by copyright. All rights reserved.

Role of Bi-Weekly Serum Galactomannan Screening for the Diagnosis of Invasive Aspergillosis in Hematologic Cancer Patients

Summary

Invasive aspergillosis (IA) is a life-threatening infection affecting hematologic cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been proposed for a preemptive therapeutic approach of IA in patients not receiving mold-active prophylaxis. We have analyzed all IA cases among patients with hematologic malignancies and prolonged chemotherapy-induced neutropenia (>14 days) in our institution over a 10-year period (2007-2017). Serum GM was measured twice weekly and mold-active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12-week survival versus 100% among serum GM-negative patients, p=0.006), irrespective of the timing of GM positivity compared to CT. We concluded that bi-weekly serum GM screening demonstrated limited benefit in this population.

This article is protected by copyright. All rights reserved.

Fungal infections in patients with inflammatory bowel disease: a systematic review

Summary

Background

Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown.

Objectives

The aim of this systematic review is to examine all available evidence regarding fungal infections in patients with IBD.

Methods

Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into three categories: a) characteristics of fungal infections; b) data on IBD; and c) treatment and outcomes of fungal infections in patients with IBD.

Results

Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used.

Conclusions

This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

This article is protected by copyright. All rights reserved.

Comorbidities of pyoderma gangrenosum: a retrospective multicentric analysis of 126 patients

Abstract

Pyoderma Grangrenosum (PG) is a rare neutrophilic dermatosis with challenging diagnosis and unclear underlying mechanisms. Multifactorial causes are purposed, including neutrophilic dysfunction, aberrant cellular immunity and cytokinic activities, and genetic predispositions¹. An association with a systemic disease is classically described in 25 to 75% of cases, including inflammatory bowel diseases (IBD), inflammatory rheumatological diseases (IRD) and hematological disorders. Association of PG with cardiovascular disorders have also been proposed ^2,3. Due to its rarity, the literature on PG-associated comorbidities remains limited to date.

This article is protected by copyright. All rights reserved.

Defective RNA sensing by RIG-I in severe influenza virus infection

Summary

Influenza virus infection causes worldwide seasonal epidemics. Although influenza usually is a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in antiviral responses during influenza. However, IFN regulatory factor (IRF)7 deficiency is so far the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 Swine Flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the CARD and RNA binding domains, respectively, of DDX58 encoding the RNA sensor RIG-I. These variants significantly impair the signaling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased pro-inflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought for in future studies of genetic factors influencing single-stranded RNA virus infections. This article is protected by copyright. All rights reserved.

The role of the immune system in kidney disease

Abstract

The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Though the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, eventually leading to kidney failure. As renal disease often only manifests clinically when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. This article is protected by copyright. All rights reserved.

Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing

ABSTRACT

Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. CXCR5 is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand CXCL13. We here aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5⁺ and CXCL13⁺ cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (p<0.01). Notably, a decreased percentage of CXCR5⁺ cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19⁺CD27⁺IgD⁺ marginal zone (p<0.001), CD19⁺CD27⁺IgD^- memory (p<0.05) and CD27-IgD double-negative (p<0.01) B cells, and CD4⁺CXCR3^-CCR6⁺ Th17 cells (p<0.05). CXCL13 levels were increased in patient plasma (p<0.001), and immunohistochemical staining revealed expression of CXCL13, and higher numbers of CXCR5⁺ cells (p<0.0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5⁺ cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS. This article is protected by copyright. All rights reserved.

Application of washed MSWI fly ash in cement composites: long-term environmental impacts

Abstract

In the present study, long-term environmental impacts of compact and ground cement composites, in which 30 wt.% of cement was replaced by washed municipal solid wastes incineration (MSWI) fly ash, were investigated for use in building industry. Consecutive leaching tests over a time span of 180 days were performed in acid water, deionized water, and saline water, respectively, with the accumulative concentration of different elements determined in the leachate. Different leaching behaviors are observed among different potential toxic elements (PTEs). For instance, higher concentrations of V in the leachate were observed from the compact cement composites than those from the ground ones. The concentration of Ba in the leachate increased with the decrease of particle size of the cement composites, and an initial increase in the leaching efficiency of Sn was followed by a clear decline with the leaching time. In addition, kinetic study revealed that the leaching behaviors of potential toxic elements follow a second-order model. The results demonstrated that the addition of washed MSWI fly ash into cement can contribute to the attrition resistance, indicating that the washed MSWI fly ash could be a promising alternative for cement as supplementary building materials.

A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma

Summary

Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed and accrual was stopped. Stable disease was noted in 6 (46%) patients, with 1 patient on study for 42 weeks. Riluzole was well-tolerated, with fatigue (62%) as the most common adverse event. MAPK and PI3K/AKT downregulation was noted in 33% of paired tumor biopsies. Hypothesis generating correlative studies suggested that downregulation of angiogenic markers and increased leuckocytes at the active edge of tumor correlate with clinical benefit. Pharmacokinetic analysis showed inter-patient variability consistent with prior riluzole studies. Future investigations should interrogate mechanisms of biologic activity and advance development of agents with improved bioavailability.

This article is protected by copyright. All rights reserved.

Liver disturbances in activated phosphoinositide 3-kinase δ syndrome

Publication date: Available online 16 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Gil Ben-Yakov, Devika Kapuria, Jamie Marko, Min Ho Cho, Stefania Pittaluga, David Erwin Kleiner, Christopher Koh, Steven Holland, Gulbu Uzel, Theo Heller

Syndromic sebaceous nevus: current findings

Abstract

Background

Sebaceous nevus is a congenital malformation of the skin that usually occurs on the scalp or face. Syndromic forms do rarely exist with associated cerebral and ocular malformations. The skin lesions are pale at birth and become irregular by puberty. In the adult patient, tumors (usually benign) develop from sebaceous nevus. Their surgical excision during childhood can give a better result in terms of the definitive scar.

Objectives

The aim of this study is to analyze our cases of syndromic sebaceous hamartoma, perform a review of the existing literature, and propose guidelines for the therapeutic plan.

Methods

This is a retrospective study reviewing the cases of syndromic sebaceous nevus treated in the Department of Orthopedic Plastic Pediatric Surgery in Montpellier, France, and the Department of Pediatric Surgery in Lausanne, Switzerland, between 1994 and 2016.

Results

The files of six patients with syndromic sebaceous nevus were analyzed. The average age at the first consultation was 4 months. The location was craniofacial in all cases. Cerebral radiological imaging was performed on all patients; two showed abnormal findings. Four patients underwent ophthalmic examination, which all revealed abnormalities. Three patients had other associated malformations. Three patients presented with epilepsy or learning difficulties in the course of follow-up.

Conclusion

All patients presenting with extensive sebaceous nevus of the craniofacial region should benefit from cerebral imagery and ophthalmic examination since there is a very high probability of associated abnormalities. The developmental problems encountered could not be definitively associated with the skin malformations.