Editorial Board

Neurosurgeons still wanted

It is tempting to speculate that advances in molecularly targeted therapy might diminish the important role that surgeons have always played in the care of patients with glioblastoma (GBM). Maximum safe resection of at least the contrast-enhancing portion of the tumor mass is the desired starting point for treatment regimens in modern neuro-oncology. Surgical excision of >70% of the enhancing tumor volume significantly prolongs the overall survival of patients with GBM who are treated with the proven combination of external-beam radiation and temozolomide chemotherapy after initial diagnosis.^1–3 We do not know, however, whether the survival advantage associated with surgery observed in the radiation–temozolomide era of neuro-oncology will carry over into the future as highly selective anticancer drugs and immunotherapy agents emerge from the development pipeline and enter the clinic. The results of the study published by Ellingson and colleagues indicate that neurosurgeons will likely remain an effective strike force in the war on GBM even as medical treatment methods improve.⁴

Nomograms based on Pre-operative Multi-parametric Magnetic Resonance Imaging for Prediction of Molecular Subgrouping in Medulloblastoma: Results from a Radiogenomics Study of 111 Patients

Abstract

Background

Novel biological insights have led to consensus classification of medulloblastoma into four distinct molecular subgroups – wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We aimed to predict molecular subgrouping in medulloblastoma based on pre-operative multi-parametric magnetic resonance imaging (MRI) characteristics.

Methods

A set of 19 MRI features were evaluated in 111 patients with histologic diagnosis of medulloblastoma for prediction of molecular subgrouping. MRI characteristics were correlated with molecular subgroups derived from tissue samples in 111 patients (WNT=17, SHH=44, Group 3=27, and Group 4=23). Multinomial logistic regression of imaging parameters was performed on a training cohort (TC) of 76 patients, representing two-thirds of randomly-selected patients from each of four molecular subgroups, to generate binary nomograms. Validation of these nomograms was performed on the remaining 35 patients as the validation cohort (VC).

Results

Medulloblastoma subgroups could be accurately predicted by pre-operative MRI features in 74% of cases. Predictive accuracy was excellent for SHH (95%), acceptably high for Group 4 (78%), modest for Group 3 (56%) and worst for WNT (41%) subgroup medulloblastoma. SHH-specific nomogram was associated with excellent correlation between TC and VC, with area under the curve (AUC) of 0.939 and 0.991 respectively. AUC for Group 4 was acceptable at 0.851 and 0.788 in TC and VC respectively; however, these values were consistently suboptimal in WNT and Group 3 medulloblastoma.

Conclusion

The predictive accuracy of MRI-based nomograms was excellent for SHH and encouraging for Group 4 medulloblastoma. Further work is needed for Group 3 and WNT-pathway medulloblastoma.

Survivorship in Adults with Malignant Brain and other Central Nervous System Tumor from 2000-2014

Abstract

Background

The goal of this study was to provide up to date and comprehensive statistics on incidence, survival, and prevalence rates for selected malignant brain and other CNS tumors in adults.

Methods

The current study used CBTRUS data, provided by CDC, to examine incidence and SEER data to examine survival and prevalence in sixteen distinct malignant brain and other CNS histologies in adults (aged 20 years and older at diagnosis) from 2000-2014 overall and by sex, age group, race, and ethnicity.

Results

Glioblastoma had the highest incidence (4.40 per 100,000) and prevalence (9.23 per 100,000). Ependymal tumors had the highest 5- and 10-year relative survival (87.8% and 84.5%, respectively), while glioblastoma had the lowest 5- and 10-year relative survival (5.4% and 2.7%, respectively). Females generally had better survival and lower prevalence than males. Younger adults tended to have better survival than older adults, and prevalence varied greatly by age and histology. While survival did not vary significantly by race, White adults had higher prevalence than the other race groups. Hispanics generally had better survival rates and lower prevalence than non-Hispanics.

Conclusions

Survival varied greatly by age and ethnicity. Prevalence differed by sex, age, race, and ethnicity.

Occurrence and distribution of antibiotics in surface water impacted by crab culturing: a case study of Lake Guchenghu, China

Abstract

The objective of this study was to evaluate the occurrence, distribution, potential sources, and ecological risk of antibiotics in aqueous phase of Lake Guchenghu, China. Target antibiotics in surface water of Lake Guchenghu, adjacent streams, and crab ponds were detected seasonally. The results showed that erythromycin-H₂O (1.60–2450 ng/L), sulfadiazine (ND–654 ng/L), and florfenicol (ND–919 ng/L) were the predominant antibiotics in Lake Guchenghu. The concentrations of antibiotics in Lake Guchenghu Basin showed obvious seasonal variation, with the highest concentration in summer. In general, the concentrations of antibiotics in crab ponds and streams were higher than those in the lake and spatial distributions of antibiotics were affected by pollution sources. The types and origins of antibiotics indicated that wastewater from ponds was the main source of antibiotics in the lake. Risk assessment suggested that as individual compound, erythromycin-H₂O and clarithromycin posed a high risk to algae while other compounds might pose low or no risk. The mixture of antibiotics may pose a high risk to aquatic organisms in Lake Guchenghu. Overall, our study revealed the occurrence and spatiotemporal variation of antibiotics in Lake Guchenghu, which was related with crab culturing.

Effectiveness of transcutaneous electrical nerve stimulation for the treatment of migraine: a meta-analysis of randomized controlled trials

Migraine is now ranked as the second most disabling disorder worldwide reported by the Global Burden of Disease Study 2016. As a noninvasive neurostimulation technique, transcutaneous electrical nerve stimulat...

Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation

Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown.

Ablative fractional laser-assisted photodynamic therapy provides superior long-term efficacy compared to standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen’s disease

Ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12 months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen's disease (BD). However, long-term follow-up data are not available.

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study

Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.

A Step Toward Demystifying Melanomas of Unknown Primary Sites

Management of primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma: A retrospective study

Hierarchical protein export mechanism of the bacterial flagellar type III protein export apparatus

Abstract

The bacterial flagellum is supramolecular motility machinery consisting of the basal body, the hook and the filament. Flagellar proteins are translocated across the cytoplasmic membrane via a type III protein export apparatus, diffuse down the central channel of the growing structure and assemble at the distal end. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. The completion of hook assembly is the most important morphological checkpoint of the sequential flagellar assembly process. When the hook reaches its mature length of about 55 nm in Salmonella enterica, the type III protein export apparatus switches export specificity from proteins required for the structure and assembly of the hook to those responsible for filament assembly, thereby terminating hook assembly and initiating filament assembly. Three flagellar proteins, namely FliK, FlhB and FlhA, are responsible for this substrate specificity switching. Upon completion of the switching event, interactions among FlhA, the cytoplasmic ATPase complex and flagellar type III export chaperones establish the assembly order of the filament at the hook tip. Here, we describe our current understanding of a hierarchical protein export mechanism used in flagellar type III protein export.

Fatty acids and their amide derivatives from endophytes: new therapeutic possibilities from a hidden source

Abstract

Fatty acid and their amide derivatives are natural self-defense agents in plants. They have been observed to be broadly bioactive against a variety of disease agents. The mechanism of action understood so far being their targeting the protein synthesis and causing leakage of the intracellular components. Owing to their broad bioactivity, the fatty acids and their amides as therapeutics can cover a wide range of indications such as cancer, bacterial infections, parasitic infection, inflammations, diabetes and obesity to name a few. The microorganisms residing inside the healthy plant tissues are a unique niche for exploration of novel bioactive compounds. The recent identification of fatty acid amide derivatives as well as prior reports from endophytes have drawn fresh attention to this unique source for their isolation. Hence, they represent an exciting opportunity for the development of new therapeutic agents against existing disease causative agents. In this paper, we will discuss the production of fatty acids and amide derivatives by plants and their associated endophytes. Their reported bioactivities establishing their potential benefit as possible therapeutic agents will also be examined.

Contamination levels and health risk assessments of heavy metals in an oasis-desert zone: a case study in northwest China

Abstract

Rapid and extensive social and economic development has caused severe soil contamination by heavy metals in China. The spatial distribution, pollution levels, and health risks of metals were identified in an oasis-desert zone of northwest China. The mean concentrations of six heavy metals exceeded their corresponding background contents, and each metal concentration in farmland samples was higher than that in Gobi samples. Moreover, these heavy metals followed a similar spatial pattern and showed significant positive correlations with each other, indicating that they have the same sources. The contamination features of heavy metals and ecological risks were calculated using several quality indicators, and their health risks for population groups were quantified. The results showed that the Gobi and farmland soils were uncontaminated to moderately contaminated by heavy metals, and that farmland pollution was more serious than that of Gobi. The Gobi and farmland soils posed low ecological risks. As a whole, the non-carcinogenic risk which was caused by heavy metals was low for local residents, and the carcinogenic risk was within an acceptable level. Comparatively speaking, children were the more vulnerable population to health risks. The Zn and Cu pollution was relatively serious, and Cr and V were major contributors to health risks.

Graphical abstract

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Combined toxicity of chlorantraniliprole, lambda-cyhalothrin, and imidacloprid to the silkworm Bombyx mori (Lepidoptera: Bombycidae)

Abstract

Insecticides with different modes of action may act in combination, in ways such as drifting, spray equipment residual, or utilizing concurrently in mulberry orchards or nearby agricultural fields. Silkworms may suffer from a diverse impact on the survival. In this study, the toxicity of chlorantraniliprole, lambda-cyhalothrin, and imidacloprid and their combinations to the second instar of silkworms (Bombyx mori (L.)(Lepidoptera: Bombycidae)) were evaluated after 48 and 72 h treatment by the leaf-dipping method and the combination index (CI)-isobologram equation. After 48 h treatment, results indicated that (1) the increasing order of toxicity was imidacloprid < chlorantraniliprole < lambda-cyhalothrin, and that (2) synergism was predominated in most combinations excepted for the lambda-cyhalothrin + imidacloprid combination which displayed an additive effect at f_a value 0.5. Then, after 72 h treatment, results exhibited that (1) the increasing order of toxicity was imidacloprid < lambda-cyhalothrin < chlorantraniliprole, and that (2) only the chlorantraniliprole + imidacloprid mixture yielded antagonism at f_a value 0.5; the other combinations performed an additive effect at least. Consequently, combined toxicity of mixtures may pose a worse effect on silkworm than single toxicity of insecticides. Therefore, we suggest that insecticide mixtures should be added into ecotoxicological risk assessment.

Monitoring and spatiotemporal variations of pyrethroid insecticides in surface water, sediment, and fish of the river Chenab Pakistan

Abstract

There is a serious concern regarding freshwater resources of Pakistan which have been mismanaged and now are depleting extensively due to other reasons like intensive application of agricultural pesticides and insecticides. The present study was conducted to determine the concentrations of cypermethrin, deltamethrin, permethrin, and bifenthrin in the samples of water, sediments, and fish collected from various locations of River Chenab, Pakistan, during summer and winter seasons. These locations include namely Marala, Khanki, Qadirabad, and Trimu Headworks. High-performance liquid chromatography (HPLC) was deployed for analysis and determination of pyrethroid concentrations in these samples. The analytics show the order of pyrethroid concentrations in river as fish> sediment>water. Whereas maximum concentrations of 0.472 μg g⁻¹ found in fish and minimum concentrations were determined in water, i.e., 0.087 μg L⁻¹ at the sampling locations of Trimu and Marala headworks, respectively. Moreover, highest mean concentrations of pyrethroid, i.e., 1.248 μg g⁻¹ in fish were detected in winter season as compared to summers, i.e., 0.087 μg L⁻¹. However, all the values of pyrethroid were found to be lower than the maximum permissible levels specified by EU and WHO-FAO. Whereas the levels of deltamethrin and permethrin in water were found much higher than the specific limits set by EU.

Mortality in women treated with assisted reproductive technology treatment – addressing the healthy patient effect

Abstract

Previous studies have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. The aim of this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994–2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until ultimo 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women immediately after ART treatment (HR = 0.68, 95% CI: 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with a markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequency of previous medical and psychiatric diagnoses among ART-treated and untreated women was similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make ART treatment initiation unlikely. The survival advantage among ART-treated women is likely a selection rather than a biological phenomenon.

What makes an animal? The molecular quest for the origin of the Animal Kingdom

Synopsis

What makes an animal? To find the answer we need to integrate data from disciplines such as phylogenetics, palaeontology, ecology, development, anatomy and physiology, as well as molecular biology and genomics. Knowledge of which groups branched before and after the origin of animals is essential. Recent advances in molecular phylogenetics, together with the discovery of new eukaryotic lineages, have drawn a new picture of the ancestry of animals. The nature of the early diverging animal lineages and the timing of the transition are in a state of flux. Various factors have been linked to this striking transition to multicellularity, including changes in environmental conditions and the ecological interactions between unicellular eukaryotes. The current wealth of genomic data has also shed new light on this question. The analysis of the genome of various close relatives of animals has revealed the importance that recycling of ancient genes into metazoan biological functions played into animal origins. A recent study reconstructing the genome of the last common ancestor of extant animals has unveiled an unprecedented emergence of new genes, highlighting the role of genomic novelty in the origin of metazoans.

Insights into electroreceptor development and evolution from molecular comparisons with hair cells

Synopsis

The vertebrate lateral line system comprises a mechanosensory division, with neuromasts containing hair cells that detect local water movement ("distant touch"); and an electrosensory division, with electrosensory organs that detect the weak, low-frequency electric fields surrounding other animals in water (primarily used for hunting). The entire lateral line system was lost in the amniote lineage with the transition to fully terrestrial life; the electrosensory division was lost independently in several lineages, including the ancestors of frogs and of teleost fishes. (Electroreception with different characteristics subsequently evolved independently within two teleost lineages.) Recent gene expression studies in a non-teleost actinopterygian fish suggest that electroreceptor ribbon synapses employ the same transmission mechanisms as hair cell ribbon synapses, and show that developing electrosensory organs express transcription factors essential for hair cell development, including Atoh1 and Pou4f3. Previous hypotheses for electroreceptor evolution suggest either that electroreceptors and hair cells evolved independently in the vertebrate ancestor from a common ciliated secondary cell, or that electroreceptors evolved from hair cells. The close developmental and putative physiological similarities implied by the gene expression data support the latter hypothesis, i.e., that electroreceptors evolved in the vertebrate ancestor as a "sister cell-type" to lateral line hair cells.

IDH-mutation Status is Associated with Distinct Vascular Gene Expression Signatures in Lower Grade Gliomas

Abstract

Background

Vascular gene expression patterns in lower grade gliomas (LGG, diffuse WHO grade II-III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH)-mutation status affects vascular phenotype.

Methods

Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the TCGA database. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grade II-IV gliomas and non-malignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro.

Results

Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of LAMA4 and ANGPT2 in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including up-regulation of ANGPT2 and SERPINH, connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased TGFβ and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was up-regulated by stimulation of endothelial cells with TGFβ2, VEGF or CoCl₂in vitro.

Conclusion

IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGF and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.

Bullous complex regional pain syndrome: A description of the clinical and histopathologic features

Journal of Cutaneous Pathology, EarlyView.

Impact of a static magnetic field on biodegradation of wastewater compounds and bacteria recombination

Abstract

The current study presents results concerning the effect of a static magnetic field (SMF) on synthetic wastewater biodegradation by activated sludge and on dehydrogenase activity of microorganisms of activated sludge. The highest process efficiency was obtained for a SMF of 0.0075 T among the tested magnetic flux density values of 0.005–0.14 T. Decrease in COD was 25% higher for the bioreactor exposed to SMF compared with control experiments. The positive effect of SMF 0.0075–0.0080 T was confirmed in experiments on the dehydrogenase activity of activated sludge. It was also shown that a SMF of 0.007 T increased p-nitroaniline removal from wastewater and influenced the recombination frequency in a streptomycin-resistant bacteria strain of Eschercihia coli.