The Role of the Specialist Nurse in Gynaecological Cancer

Abstract

Purpose of Review

To explore the role of the specialist nurse within gynaecological cancer.

Recent Findings

There are many different job titles associated with the role of the specialist nurse. Nursing roles are evolving not only to meet the increasing demands on services but also within the ever changing landscape of cancer treatments and improvement in survival. Women and their families need specialist nurses to guide and support them on their cancer journey, along the treatment trajectory and into survivorship.

Summary

This paper explores specialist nurse roles generally, and within our service which have been adapted to meet service and patient needs within a gynaecological cancer centre. Irrelevant of title, specialist nurses are best suited to meet the patients' needs. The fundamental ethos of the care should always remain having the patients' best interest at heart, acting as their advocate - in essence giving them a voice when they need it.

Evaluating the Use of 18F-FDG PET CT for External Beam Radiotherapy Planning in Gynaecological Malignancies

Abstract

Purpose of Review

To evaluate the evidence for the use of fluorine-18-fluorodeoyglucose (18F-FDG) PET CT in external beam radiotherapy planning for treatment of gynaecological malignancies.

Recent Findings

Our review confirms that the incorporation of 18F-FDG PET CT during radiotherapy planning may decrease inter-observer variability during target delineation. It can also provide useful functional information regarding the tumour, which may facilitate the development of techniques for dose escalation and 'dose painting' not only for primary disease, especially in cervical cancer, but also nodal metastasis.

Summary

The utilisation of this functional modality in external beam radiotherapy planning, particularly in locally advanced cervical malignancy, is an exciting topic that warrants further prospective research. Perhaps the most valuable role may be the potential to deliver dose escalation to 18F-FDG PET CT avid targets previously limited by organ at risk constraints, now that we have significantly more advanced radiotherapy planning tools at our disposal.

Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly

Abstract

Most common thyroid cancers are differentiated thyroid cancers (DTCs) and have papillary, follicular, or Hürthle cell morphology. Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. The incidence of DTC increases with age. While most of the patients with DTC have an excellent prognosis, the outcome can be poor when diagnosed in elderly patients.

Purpose of Review

Current treatment approach for DTC includes surgery, thyroid-stimulating hormone (TSH) suppression, radioactive iodine, external beam radiotherapy, or systemic treatments such as kinase inhibitors. Radioactive iodine therapy (RAI) is the primary first-line systemic treatment for advanced DTC. However, during the course of treatment, the tumor may become refractory to RAI. Elderly patients are more likely to be diagnosed with advanced disease that can be refractory to RAI.

Recent Findings

The advent of TKIs (tyrosine kinase inhibitors) and their usage in RAI refractory disease has shown improved progression-free survival. These agents are, however, associated with increased toxicity.

Summary

The variable nature of disease and toxicity associated with the systemic therapy makes it important to have an individualized approach to management, especially in the elderly population who can be more susceptible to toxicities.

Characterization of bacterial and microbial eukaryotic communities associated with an ephemeral hypoxia event in Taihu Lake, a shallow eutrophic Chinese lake

Abstract

While the important roles of microbial communities in oceanic hypoxic zones were beginning to be understood, little is known about microbial community associated with this phenomenon in shallow lakes. To address this deficit, both the bacterial and microbial eukaryotic communities of an ephemeral hypoxic area of Taihu Lake were characterized. The hypoxia provided nutritional niches for various bacteria, which results in high abundance and diversity. Specific bacterial groups, such as vadinBC27 subgroup of Bacteroidetes, Burkholderiales, Rhodocyclales, Pseudomonas, and Parcubacteria, were dominated in hypoxic sites and relevant to the fermentation, denitrification, nitrification, and sulfur metabolism. Conversely, most of microbial eukaryotes disappeared along with the decline of DO. An unexpected dominance of fungi was observed during hypoxia, which partly explained by the accumulation of toxic algae. Mucor was the single dominant genus in the hypoxic zone. We proposed that this group might cooperate with bacterial communities in the anaerobic degradation of algal biomass and woody materials. Generally, the hypoxic microbiome in shallow lakes is mainly involved in fermentative metabolism depending on phytodetritus and is potentially influenced by terrestrial sources. This study provided new insights into the unique microbiome in short-term hypoxia in shallow lakes and lays the foundation for studies that will enhance our understanding of the microbial players associated with hypoxia and their adaption strategy on the global scale.

TUEF2016-environmental pollution: problem and solution

Distinguishing histopathologic features of acantholytic dermatoses and the pattern of acantholytic hypergranulosis

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.

Anti‐inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model

Journal of Cosmetic Dermatology, EarlyView.

Minimally invasive approaches to axillary osmidrosis treatment: A comparison between superficial liposuction with automatic shaver curettage, subcutaneous laser treatment, and microwave‐based therapy with a modified technique

Journal of Cosmetic Dermatology, EarlyView.

Lead exposure from households and school settings: influence of diet on blood lead levels

Abstract

Lead is known as a potent toxicant to human health, particularly for children while their central nervous system is developing. The aim of this study was to investigate the associations between blood lead levels (BLLs) and lead exposure in the children's diet, home, and school environments. A cross-sectional study was conducted with 153 children aged 1–4 years, in four day care centers (DCCs), where a high prevalence of lead exposure was previously found. Lead determination by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64). Environmental screenings were conducted to evaluate lead concentrations in the tableware, buildings, and playground items in all DCCs and children's homes (n = 18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean was 2.71 μg dL⁻¹. Means for 24-h lead concentrations in the diet were 1.61 and 2.24 μg kg⁻¹ of body weight (BW) in two DCCs. Lead concentrations in the water supply were lower than 2 μg L⁻¹. More than 11% of the DCCs' environmental analyses presented lead concentrations higher than or equal to 1 mg cm⁻², as defined by the USEPA. The diet was not found to be a risk factor for lead exposure, but households and DCC settings raised concern. Children's exposure to lead in DCC environments, where they spend the most part of their weekdays, appeared to be relevant.

Graphical abstract

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Adsorption of basic and reactive dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon: batch and column study

Abstract

The adsorption behavior of basic, methylene blue (MB), and reactive, remazol brilliant violet 5R (RBV), dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon (IBSAC) was executed via batch and column studies. The produced activated carbon was characterized through Brunauer-Emmett-Teller (BET) surface area and pore structural analysis, proximate and ultimate, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). Batch studies were performed to investigate the effects of contact time, initial concentration, and solution pH. The equilibrium data for both MB and RBV adsorption better fits Langmuir model with maximum adsorption capacity of 434.78 and 212.77 mg/g, respectively. Kinetic studies for both MB and RBV dyes showed that the adsorption process followed a pseudo-second-order and intraparticle diffusion kinetic models. For column mode, the breakthrough curves were plotted by varying the flow rate, bed height, and initial concentration and the breakthrough data were best correlated with the Yoon-Nelson model compared to Thomas and Adams-Bohart model. The adsorption activity of IBSAC shows good stability even after four consecutive cycles.

Roles of hydrophobic and hydrophilic fractions of dissolved organic matter in sorption of ketoprofen to biochars

Abstract

Hydrophobic acid (HoA) and hydrophilic neutral (HiN) are two major fractions of dissolved organic matter (DOM). Their role in the sorption of ketoprofen (KTP) to wheat straw-derived biochars pyrolyzed at 300 °C (WS300) and 700 °C (WS700) was investigated to further probe the mechanisms responsible. WS700 has much higher pore volume and specific surface area (SSA) than WS300. Loading of HoA and HiN resulted in surface coverage of biochars. HoA with larger molecular size led to more pore blockage of biochars than HiN. Higher HoA binding affinity also caused a stronger competition with KTP on biochars. These factors reduced the accessibility of sorption sites for KTP, and significantly inhibited KTP sorption to biochar of lower SSA (i.e., WS300) by HoA. Water solubility (S_w) of KTP was slightly enhanced (3%) in the presence of HoA. In contrast, the presence of HiN reduced (22%) S_w of KTP. The decreased S_w of KTP by HiN exerted a more dominant influence than its competitive and loading effects, thus led to apparent enhanced sorption of KTP, especially to biochar of higher SSA (i.e., WS700). The results demonstrated the diverse effects of HoA and HiN on KTP sorption, which is helpful in understanding pharmaceutical-DOM-biochar interactions and environmental behaviors of pharmaceuticals.

Utilization of freshwater mussel ( Lamellidens marginalis ) for the isolation of proteins through pH shift processing: characterization of isolates

Abstract

Study was conducted to use underutilized freshwater mussel (Lamellidens marginalis) for the recovery of proteins using pH shift method and to study the functionality and characteristics of the recovered isolates. From the pH range tested (pH 2.0–13.0), maximum protein yields were obtained during solubilization at pH 2.0 and pH 13.0 (p < 0.05). During the protein recovery process, pH 13.0 was found to have minimal effect on proteins resulting in higher protein yields compared to pH 2.0. Isolates obtained by both acidic and alkaline solubilization processes had low stability and poor gel network. Total lipid content, total myoglobin, and pigment contents were reduced significantly (p < 0.05) during pH shift processing, resulting in whiter protein isolates and protein gels. All the essential amino acids were present in the isolates recovered by acid and alkaline solubilization, indicating the complete recovery of amino acids. No microbial counts were observed in any of the isolates prepared using acid and alkaline-aided processing. Acid and alkaline solubilization (pH shift) process was found to be promising for the recovery of proteins from underutilized freshwater mussel thus by reducing the supply demand gap.

Air pollution control and flue gas desulfurization residues from Polish copper smelting facility as adsorbents of Pb(II) and Cu(II) from aqueous solutions

Abstract

This study aimed at evaluation of air pollution control residues (APCR) and flue gas desulfurization residues (FGDR) from copper foundry in Southwestern Poland as adsorbents of Cu(II) and Pb(II) from simulated wastewater. Studies of the impact of pH and adsorbent dose, as well as sorption isotherms, and kinetic and thermodynamic studies were conducted in a series of batch experiments. The maximum adsorption capacities were equal to 42.9 mg g⁻¹ Cu(II) and 124.4 mg g⁻¹ Pb(II) for APCR and 98.8 mg g⁻¹ Cu(II) and 124.7 mg g⁻¹ Pb(II) for FGDR, which was comparable to mineral adsorbents examined in other studies. Adsorption isotherms followed the Langmuir model, except for Pb(II) for FGDR, which followed Freundlich model. Sorption kinetics for both materials was properly expressed by pseudo-second-order equation. Mean adsorption energy parameter suggested that the adsorption might have occurred via physical bonding. Thermodynamic study revealed that adsorption was spontaneous and endothermic for Cu(II) and not spontaneous and exothermic for Pb(II), with lower temperature favoring the process. The results suggested that both materials had high affinity towards Cu(II) and Pb(II) ions and could be conducted industrial scale research for consideration as potential adsorbents from aqueous solutions.

Selected trace elements and metals in groundwater within Permian sediments near Olkusz (Zn-Pb ore mining region, S Poland)

Abstract

The extensive mining of Zn-Pb ores in the Olkusz region resulted in significant changes of both water table level and chemical composition of water in all aquifers in the area. This was caused by intensive dewatering of mining excavations and development of a thick aeration zone reaching 150 m in a central part of the area. That created favorable conditions for oxidation of metal sulfides occurring in the ore-bearing dolomites (Middle Triassic) and started the process of forming readily soluble hydroxysulphates which then migrated to lower aquifers, including the Permian. As a result of those processes, various metals and other elements toxic to the water environment appeared in leaks observed in mine galleries. Changes in concentrations of selected elements (Fe, Mn, Zn, Pb, Cu, Ba, Ni, Co, As, Cr, Hg, Tl, Ag, Cd, B) in mine waters over the period of the last nearly 50 years were described. Water samples were collected from exploratory boreholes, piezometers, and wells located in investigated area inflows and seepages occurring in shafts and drifts excavated in Permian conglomerates. Mean concentrations of metals (Pb, Cd, Cr, Hg, Tl) and other toxic elements were surprisingly low; Pb, 3.94 μg/L; Cd, 0.2 μg/L; Cr, up to 2.26 μg/L; Hg, 0.25 μg/L; Tl, 3.59 μg/L; and As, 6.31 μg/L. However, the observed concentrations varied significantly over time, reaching respectively up to 190 μg Pb/L, 60 μg Cd/L, 15.6 μg Cr/L, 2.67 μg Hg/L, 81.3 μg Tl/L, and 155 μg As/L.

Loss of Biodiversity Dimensions through Shifting Climates and Ancient Mass Extinctions

Abstract

Many aspects of climate affect the deployment of biodiversity in time and space, and so changes in climate might be expected to drive regional and global extinction of both taxa and their ecological functions. Here we examine the association of past climate changes with extinction in marine bivalves, which are increasingly used as a model system for macroecological and macroevolutionary analysis. Focusing on the Cenozoic Era (66 Myr ago to the present), we analyze extinction patterns in shallow-water marine bivalve genera relative to temperature dynamics as estimated from isotopic data in microfossils. When the entire Cenozoic timeseries is considered, extinction intensity is not significantly associated with the mean temperature or the detrended variance in temperature within a given time interval (stratigraphic stage). However, extinction increases significantly with both the rate of temperature change within the stage of extinction and the absolute change in mean temperature from the preceding stage to the stage of extinction. Thus, several extinction events, particularly the extinction pulse near the Pliocene–Pleistocene boundary, do appear to have climatic drivers. Further, the latitudinal diversity gradient today and the Cenozoic history of polar faunas suggest that long-term, regional extinctions associated with cooling removed not just taxa but a variety of ecological functions from high-latitude seas. These dynamics of biodiversity loss contrast with the two mass extinctions bracketing the Mesozoic Era, which had negligible effects on the diversity of ecological functions despite removing nearly as many taxa as the latitudinal gradient does today. Thus, the fossil record raises a key issue: whether the biotic consequences of present-day stresses will more closely resemble the long-term effects of past climate changes or those that cascaded from the mass extinctions.

Where Animation and Science Meet

Synopsis

Animation is the collision of art and science. How does an animation studio like DreamWorks Animation use scientific principles and engage in science education to make our films better? By facilitating scientific master-classes, demos, and lectures we give our creators a fundamental understanding of reality that enables them to create the animation caricature known as the Illusion of Life. We leverage principles of biology and physics to create believable performances. I will share insights about our custom programming such as master-classes on Quadruped Anatomy and Flight and how these result in a better image on screen. Conversely, animators offer storytelling tools to the scientific community. Animators often use visualization tools similar to those that many scientists use, but in differing narrative orders and with budgets often far exceeding those of scientists. I will highlight strategies of presentation enhancing understanding and increasing the speed of building bridges to share information with the public. This can help scientists leverage their own scientific principles as they present the importance and excitement of their work to the public, as well as to one another.

The association between migraine and physical exercise

There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role ...

Patients’ perspective on the burden of migraine in Europe: a cross-sectional analysis of survey data in France, Germany, Italy, Spain, and the United Kingdom

Migraine is a distinct neurological disease that imposes a significant burden on patients, society, and the healthcare system. This study aimed to characterize the incremental burden of migraine in individuals...

Validation of a self-reported instrument to assess work-related difficulties in patients with migraine: the HEADWORK questionnaire

The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as "reduced ability to work as usual", which do not capture at a...

Myofascial trigger points in migraine and tension-type headache

A myofascial trigger point is defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. It has been suggested that myofascial trigger points t...

Correction to: Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC)

Following the publication of this article [1], the authors noticed that they incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contracept...

Phototoxicity of flavoprotein miniSOG induced by bioluminescence resonance energy transfer in genetically encoded system NanoLuc-miniSOG is comparable with its LED-excited phototoxicity

Publication date: Available online 10 September 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): G.M. Proshkina, E.I. Shramova, O.N. Shilova, A.V. Ryabova, S.M. Deyev

Abstract

Photodynamic therapy (PDT) is a clinical, minimally invasive method for destroying cancer cells in the presence of a photosensitizer, oxygen, and a light source. The main obstacle for the PDT treatment of deep tumors is a strong reduction of the excitation light intensity as a result of its refraction, reflection, and absorption by biological tissues. Internal light sources based on bioluminescence resonance energy transfer can be a solution of this problem. Here we show that luciferase NanoLuc being expressed as a fusion protein with phototoxic flavoprotein miniSOG in cancer cells in the presence of furimazine (highly specific NanoLuc substrate) induces a photodynamic effect of miniSOG comparable with its LED-excited (Light Emitting Diode) phototoxicity. Luminescence systems based on furimazine and hybrid protein NanoLuc-miniSOG targeted to mitochondria or cellular membranes possess the similar energy transfer efficiencies and similar BRET-induced cytotoxic effects on cancer cells, though the mechanisms of BRET-induced cell death are different. As the main components of the proposed system for BRET-mediated PDT are genetically encoded (luciferase and phototoxic protein), this system can potentially be delivered to any site in the organism and thus may be considered as a promising approach for simultaneous delivery of light source and photosensitizer in deep-lying tumors and metastasis anywhere in the body.

Graphical abstract

Modelling the relationship between poverty, environment, and institutions: a panel data study

Abstract

The paper examines the relationship between poverty and CO₂ emission. We contribute by using a global panel data of 146 countries over the period 1996–2014 and by focusing on the role of institution in poverty and environmental degradation nexus. The main findings are that the non-linearity relationship between poverty and CO₂ emission could prompt a further increase in the poverty and environmental degradation. However, an increase in the institutional quality leads to a reduction in poverty and more protection to the environment. The main policy recommendation is that all countries need to improve their institutional framework so that reduction of poverty and environmental degradation can occur.

Ecological degradation of an inland river basin and an evaluation of the spatial and distance effect on willingness to pay for its improvement

Abstract

Improvements in the ecological attributes of inland rivers have been projected to provide considerable non-market benefits, and the monetary valuation of these attributes has steadily increased over the past several decades. The present study addresses the spatial heterogeneity of the public's preference for ecological attributes and the distance-decay effect of willingness to pay (WTP) to improve various attributes of the river basin. The results revealed that spatial heterogeneity exists among the individuals; for example, the respondents of Liangzhou County prefer a large improvement in the natural landscape, forest coverage, and eco-tourism and are willing to pay 491.89, 369.32, and 338.37 yuan per year, respectively, for one unit improvement in these ecological attributes. Similarly, the respondents of Jinchang County value and are willing to pay 447.60, 431.81, and 318.18 yuan for one unit improvement in tourism, forest coverage, and natural landscape, respectively. Furthermore, the results from the random parameter logit model show a significant distance-decay effect of the household WTP for ecological attributes. For example, the respondents living within 5 km of the river are willing to pay more money, that is, 832.61, 365.62, and 353.05 yuan per year for improving the natural landscape, water quantity, and grass cover, respectively. As the distance from the river increases, the corresponding WTP decreases, meaning that the respondents (users) living near the Shiyang River Basin are willing to pay more for ecological attribute improvement than those living far away from the river.

Distribution of dipeptidyl peptidase (DPP) 4, DPP5, DPP7, and DPP11 in human oral microbiota – potent biomarkers indicating presence of periodontopathic bacteria

Abstract

Dipeptidyl peptidase (DPP) 4, DPP5, DPP7, and DPP11, expressed in the periplasmic space, are crucial for energy production for Porphyromonas gingivalis, an asaccharolytic bacterium that causes periodontal disease. Bacterial DPP4 seems to be involved in regulation of blood glucose level via degradation of incretins. The present study aimed to identify four dpp orthologs in oral microbiota by database searches, and their enzymatic activities in periodontopathic and cariogenic bacteria, as well as oral specimens were determined. Search in the databases suggested that 43 species of 772 taxa possess dpp4 and other dpp genes. Most species are in the genera Bacteroides, Capnocytophaga, Porphyromonas, Prevotella, and Tannerella, indicating a limited distribution of dpp orthologs in anaerobic periodontopathic rods. In accordance with those results, activities of all four DPPs were demonstrated in P. gingivalis, Porphyromonas endodontalis, and Tannerella forsythia, while they were negligible in Treponema denticola, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. Furthermore, DPP activities were also detected in subgingival dental plaque at different intensities among individual specimens, while DPP4 activity presumably derived from human entity was solely predominant in saliva samples. These findings demonstrated that DPP activities in dental plaque serve as potent biomarkers to indicate the presence of periodontopathic bacteria

Specific detection of Lysobacter antibioticus strains in agricultural soil using PCR and real-time PCR

Abstract

Lysobacter antibioticus is an important biocontrol bacteria against phytopathogens in soil and with the ability to produce nonvolatile antimicrobial metabolites has been extensively characterised. It's important to estabilish application techniques to detect and monitor L. antibioticus directly and acurately in soil samples. We developed and tested 13 primer sets according to phenazine gene (phzA, phzB, phzD, phzF, phzS) and cyclohexanone monooxygenase gene (phzNO1), a pair of primer phzNO1 F1/phzNO1 R1 based on cyclohexanone monooxygenase (phzNO1) gene of L. antibioticus strain OH13 was selected and optimized PCR amplification conditions for rapid and accurate detection. After screening 8 strains of L. antibioticus, 2 strains of L. enzymogenes, 1 strains of L. capsici, Arthrobacterium, Bacillus, Microbacterium, Burkholderia, Pseudomonas and other bacteria strains isolated from different agricultural soils, the phzNO1 F1/phzNO1 R1 primers amplified a single PCR band about 229 bp from L. antibioticus. The detection sensitivity with primers phzNO1 F1/phzNO1 R1 was 5.14×104 fg/25μL of genomic DNA and 2.254×1010 - 2.254×1011 CFU/mL for the soil samples. Real-time fluorescent qPCR assays were to develope a specific method to monitor L. antibioticus in edatope as well as guide soil micro-ecological management.

Positive reactions to gold sodium thiosulfate in patch test panels (TRUE Test) in Japan: A multicentre study

Contact Dermatitis, EarlyView.

Anaphylaxis caused by alginate dressing

Contact Dermatitis, EarlyView.

Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

Abstract

Background

Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide.

Patients and methods

Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2:1 into training (n=1159) and testing (n=550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set.

Results

Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR–NYR), 34.2 months (31.5–NYR), and 21.1 months (17.5–25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14–0.29) and 0.40 (0.30–0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups.

Conclusions

Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design.

Trial registration

ClinicalTrials.gov: NCT01212991

Immunological differences between primary and metastatic breast cancer

Abstract

Background

Little is known about how the immune microenvironment of breast cancer evolves during disease progression.

Patients and methods

We compared tumor infiltrating lymphocyte (TIL) count, PD-L1 protein expression by immunohistochemistry and mRNA levels of 730 immune-related genes using Nanostring technology in primary and metastatic cancer samples.

Results

TIL counts and PD-L1 positivity were significantly lower in metastases. Immune cell metagenes corresponding to CD8, T-helper, T-reg, Cytotoxic T, Dendritic and Mastoid cells, and expression of 13 of 29 immuno-oncology therapeutic targets in clinical development including PD1, PD-L1, and CTLA4 were significantly lower in metastases. There was also coordinated down regulation of chemoattractant ligand/receptor pairs (CCL19/CCR7, CXCL9/CXCR3, IL15/IL15R), interferon regulated genes (STAT1, IRF-1,-4,-7, IFI-27,-35), granzyme/granulysin, MHC class I and immune proteasome (PSMB-8,-9,-10) expression in metastases. Immunotherapy response predictive signatures were also lower. The expression of macrophage markers (CD163, CCL2/CCR2, CSF1/CSFR1, CXCR4/CXCL12), pro-tumorigenic toll like receptor pathway genes (CD14/TLR-1,-2,-4,-5,-6/MyD88), HLA-E, ecto-nuclease CD73/NT5E and inhibitory complement receptors (CD-59,-55,-46) remained high in metastases and represent potential therapeutic targets.

Conclusions

Metastatic breast cancers are immunologically more inert than the corresponding primary tumors but some immune-oncology targets and macrophage and angiogenesis signatures show preserved expression and suggest therapeutic combinations for clinical testing.

Design and conduct of early clinical studies of immunotherapy agent combinations: Recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies

Abstract

The Methodology for the Development of Innovative Cancer Therapies Task Force considered aspects of the design and conduct of early studies of combinations of immunotherapy agents during their 2018 meeting. The Task Force defined the relevant data to justify combination clinical trials, which includes a robust hypothesis for the combination, pre-clinical data with evidence of efficacy and an understanding of the pharmacodynamics effects of each agent, and ideally evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is critical in early phase combination trials, and should be incorporated into trial objectives and go/no-go decisions. The Task Force also identified the need to develop assessment tools and end-points that capture the unique patterns of tumour responses to immunotherapy, including pseudoprogression and hyperprogression. At least one additional tumour measurement before baseline, and an early CT scan (at 4 weeks for example) would help define the incidence of hyperprogression, although a common definition is needed. Finally, the Task Force highlighted substantial redundancy and inefficiency in the combination immunotherapy space, and recommended the adoption of innovative trial designs.

Programmed death-ligand 1 expression in uncommon epidermal growth factor receptor mutation-positive non-small cell lung cancer

Novel Facial Cream Containing Carnosine Inhibits Formation of Advanced Glycation End-Products in Human Skin

Background: Accumulation of advanced glycation end-products (AGEs) in skin has been associated with skin aging. Inhibition of glycation of proteins of extracellular matrix may help skin texture and appearance. The objective of the study was to demonstrate the antiglycation activity of topically applied carnosine and novel facial cream (FC) containing carnosine in human skin explants ex vivo. Methods: Glycation was induced in human skin explants by methylglyoxal (MG) in culture media. FC containing carnosine (FC-CARN) or carnosine in aqueous solution (AQ-CARN) was applied topically on skin explants. Levels of AGEs carboxymethyl-lysine (CML) and pentosidine were determined in the epidermis and dermis of skin sections and were used to calculate antiglycation activity. Results: Exposure to MG led to increases in CML and pentosidine in skin explants. Antiglycation effect for AQ-CARN was CML: –64 and –41%, pentosidine: –48 and 42% in epidermis and reticular dermis respectively. Antiglycation effect for FC-CARN was CML: –150 and –122%, pentosidine: –108 and –136%, in epidermis and reticular dermis respectively. Conclusion: Topically applied carnosine protects against the glycation induced by MG. Novel FC-CARN significantly reduced levels of AGEs in both epidermis and reticular dermis in human skin explants.
Skin Pharmacol Physiol 2018;31:324–331

Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and Clinical Efficacy Assessments

Background and Aim: Acne vulgaris is a common inflammatory skin condition which is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs) are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE and minimize adverse effects. This study is aimed at developing a TRE-loaded NE (NE-TRE) and at assessing the therapeutic effects of the formulation in acne vulgaris lesions, compared to conventional 0.05% TRE emulsion. Method: The high energy emulsification method was used to make NE-TRE. After obtaining stable NE, particle characterization and physicochemical properties were evaluated under accelerated conditions. Conducting a clinical study, we compared the therapeutic effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions and porphyrin production in both sides of the face. Results and Conclusion: We successfully developed stable nanoparticles. It was a stable oil-in-water emulsion with particle size of about 150 nm, and containing circular and separated particles. In a pilot clinical study, the number of acne lesions as well as the size and intensity of porphyrin production significantly reduced after topical application of NE-TRE. This formula shows proper efficiency and good loading capacity of TRE in the drug delivery system.
Skin Pharmacol Physiol 2018;31:316–323

Eruptive hypomelanosis – First case reported outside Asia

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Tinea pedis acquired in mosques?

Mycoses, EarlyView.

Day light photodynamic therapy with BF‐200 ALA: A case series

Dermatologic Therapy, EarlyView.

Facial nevus depigmentosus getting remarkable repigmentation by treatment with a 308‐nm excimer laser: A case report

Dermatologic Therapy, EarlyView.

Stereotaktische Strahlentherapie im Stadium I des nichtkleinzelligen Lungenkarzinoms

Zusammenfassung

Die stereotaktische Strahlentherapie des nichtkleinzelligen Lungenkarzinoms im Stadium I (SBRT) hat sich als Standardbehandlung für funktionell inoperable Patienten durchgesetzt. Mit hohen lokalen Kontrollraten von regelmäßig annähernd 90 % und einem hohen krankheitsspezifischen (aktuarischen) Überleben nach 5 Jahren von etwa 75 % wurde mit der SBRT als nichtinvasiver Behandlung ein erheblicher Fortschritt erzielt. Ihre Anwendung ist mittlerweile flächendeckend etabliert, stellt jedoch hohe Ansprüche an die technisch-apparative Ausstattung und Qualitätssicherung in den einzelnen Zentren. Die Wahl entsprechender Fraktionierungsschemata hängt dabei insbesondere von der Unterscheidung zwischen zentraler und peripherer Tumorlokalisation ab. Mit entsprechend angepassten Dosisregimen ist die Behandlungsverträglichkeit insgesamt sehr gut. Bezüglich der postinterventionellen Morbidität und Mortalität ist die SBRT sublobären Resektionen bei Patienten mit fortgeschrittener COPD (Chronic Occlusive Pulmonary Disease, GOLD III oder IV) überlegen. Für das operable Stadium I zeigte sich in kleineren Kollektiven (insbesondere auch in der Auswertung von zwei abgebrochenen prospektiv-randomisierten Studien), dass die Behandlungsergebnisse der SBRT bei entsprechend limitierter klinischer Evidenz an jene von leitliniengerecht (lobär) resezierten Patienten heranreichen. Aussichtsreiche laufende klinische Studien prüfen u. a. die SBRT als Boost nach Radiochemotherapie im Stadium III sowie die Kombination von SBRT und immuntherapeutischen Ansätzen im Stadium I.

Potential of guava leaves for mitigating methane emissions and modulating ruminal fermentation characteristics and nutrient degradability

Abstract

Guava leaves (Psidium guajava, GL), a high-phenolic- and flavonoid-containing plant resource capable of substituting the high-quality forage, may help in mitigating ruminal methane (CH₄) emission without adverse impact on nutrient degradability if supplemented at an appropriate level. In order to test this hypothesis, rumen fermentation, CH₄ production, and nutrient degradability of GL either solely or as a substitute of berseem hay (Trifolium alexandrinum, BH) were evaluated in a diet containing 50:50 concentrate to roughage. Five different levels of GL (0, 12.5, 25, 37.5, and 50%) were tested in vitro after 24 h incubation using a semi-automated gas production (GP) system. The current findings indicated that merely the presence of GL resulted in significantly lower values for cumulative GP (P < 0.001), CH₄ emission (P < 0.05), truly degraded dry matter (TDDM; P < 0.001), truly degraded organic matter (TDOM; P < 0.001), and ammonia nitrogen (NH₃-N) concentration (P < 0.001); however, pH (P < 0.001) and partitioning factor (P < 0.001) were higher. The total and individual volatile fatty acid (VFA) concentrations were drastically declined with GL as compared to BH (P < 0.05). A negative linear correlation was recorded between the levels of GL and GP including CH₄ production (P < 0.05). The addition of GL up to 25% did not pose any negative effect on both TDDM and TDOM values along with NH₃-N concentration. In addition, the inclusion of GL up to 25% did not affect the total or individual VFA concentration. Conclusively, in a medium concentrate diet, use of 25% GL and 25% BH in animal diet could be a promising alternative for mitigating the CH₄ production without any deleterious effect on nutrient degradability.

The process of climate change in mass media discourse using the example of Polish and international editions of “Newsweek” magazine

Abstract

The main objective of the article is to conduct a critical media discourse analysis as presented in the Polish and international editions of the "Newsweek" magazine in the years 2001–2006 and 2012–2016; the subject of which was climate change. The introduction provides the definitions of the key terms, such as: the greenhouse effect and critical discourse analysis (CDA). The theoretical part presents the most important assumptions of the CDA and presents a characteristic of the weekly. The results of the conducted quantitative and qualitative analysis partially lead to varying conclusions. Based on the CDA, the hypothesis was assumed that more attention was provided to climate change in the international (English) edition of "Newsweek", than in the Polish-language edition. Rejected in turn was the hypothesis, according to which, more importance to climate change and their repercussions was provided in the discourse within the last 5 years of publication of the weekly than in the discourse from the years 2001–2006. As a result of comparison of both discourses, the disturbing fact that media discourse did not present and encourage among the readers an active stance in favour of the climate was noticed. It is the task of this influential weekly, the message of which reaches many people, not only to provide knowledge and shape specific values or view, but also to encourage and popularise attitudes in favour of the climate. If man wants to continue to live on earth, then one of their goals is to modify the form of discourse by entities responsible for its form.

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