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.