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Παρασκευή 13 Ιουλίου 2018

Idiopathic scrotal calcinosis: report of 2 cases, and review of pathogenesis and factors that determine patients’ acceptance of surgical treatment



Diesel oil removal by Serratia sp. W4-01 immobilized in chitosan-activated carbon beads

Abstract

Serratia sp. W4-01 was immobilized in chitosan-activated carbon beads and used for diesel oil removal. The type and concentration of chitosan, activated carbon content, and bead diameter were investigated as factors affecting diesel oil removal. The results showed that 2% (w/v) squid pen chitosan beads modified with 1% activated carbon (w/v) and with a 3-mm diameter had a good spherical shape and strength as well as diesel oil removal capability. The immobilized W4-01 cells removed more than 40% of diesel oil after 7 days when the initial diesel oil concentration was 100 to 400 mg L−1, whereas 29–36% of diesel oil was removed after 14 days when the initial concentration was 800 to 1000 mg L−1. Additionally, the immobilized cells maintained the ability to remove diesel oil over a pH range of 5–11. The addition of a biosurfactant increased the diesel oil removal from 62 to 75%. The reusability tests revealed that the ability of immobilized cells to remove diesel oil was enhanced after reuse, and 50–90% of diesel oil was removed during 2 to 12 reuse cycles. The stability and survival of W4-01 cells was confirmed by scanning electron microscopy and confocal laser scanning microscopy. The results of this study showed the potential use of W4-01 cells immobilized in chitosan-activated carbon beads for future applications in remediating diesel contamination.



Effects of phosphorus on absorption and transport of selenium in rice seedlings

Abstract

The effects of different concentrations of phosphorus (P) on absorption and transfer of selenium (Se) in rice seedlings were studied by hydroponics experiment. The interaction between iron plaque and phosphorus on absorption and transport of selenium were studied by adding a large amount of iron-induced iron plaque, to provide a theoretical basis for rational application of phosphate fertilizer in the selenium bio-strengthening process of rice. The results showed that phosphorus deficiency may result in the formation of reddish brown iron oxide coating on the root surface of rice. The formation of root iron plaque of rice is related to concentration of phosphorus, and low concentration of phosphorus (0–1.5 mmol L−1) can increase the amount of root iron plaque. Compared P deficiency culture and 2 mmol L−1 P culture, Se content in the shoots and roots decreased by 76 and 47%, respectively. Addition of Fe2+ significantly reduced biomass of shoot and had no significant effect on the roots; when the P concentration increased from 0.1 to 0.3 mmol L−1, transfer coefficient of Se decreased. Therefore, both root iron plaques induced by phosphorus deficiency and iron addition have a strong adsorption effect on selenium, which reduces the transport of selenium from the rice roots to the shoots. In the lower range of phosphorus concentration, low phosphorus can promote selenium content of rice shoot, while higher on the contrary. In the practice of rice production, proper management of phosphorus nutrient is of great significance to control selenium content in rice grain.



E. coli strain engineering for the production of advanced biopharmaceutical products

Abstract
Since the emergence of the biopharmaceutical industry in the 1980's, Escherichia coli, has played an important role in the industrial production of recombinant proteins and plasmid DNA for therapeutic use. Currently, advanced biopharmaceutical products, including rationally designed recombinant proteins and viral-vector gene therapies, offer unprecedented promise for the long-term management, and even cure of disease. As such, E. coli remains an important production host for the biopharmaceutical industry. This review provides insight into the industrially relevant strain engineering approaches used to enhance both the quantity and quality of these therapeutic products.

Insights into the phylogeny of false-branching heterocytous cyanobacteria with the description of Scytonema pachmarhiense sp. nov. isolated from Pachmarhi Biosphere Reserve, India

Abstract
A false branching cyanobacterium (strain 10A1_PS) was isolated from a freshwater body of the Pachmarhi Biosphere Reserve, India and was characterised using the polyphasic approach. The detailed morphological examination indicated that the strain belonged to the complex genus Scytonema as it exhibited typical false branching character whose frequency increased with age of the culture. As the family Scytonemataceae and the genus Scytonema has been shown to be polyphyletic in many studies, we provide deep insights into the phylogenetic complexities within the family Scytonemataceae based on 16S rRNA gene phylogeny along with complete morphological, molecular and phylogenetic characterisation of the strain. The 16S rRNA gene phylogenetic tree inferred by Bayesian Inference, Neighbor-Joining and Maximum Parsimony methods showed that the strain clustered within the Scytonema sensu stricto clade. The phylogenetic distance and the positioning of the strain clearly indicated it to be different from other Scytonema species. Further analysis using rbcL phylogeny, folded secondary structures of the 16S-23S ITS, p-distance and percentage pairwise similarity matrix clearly distinguished the strain 10A1_PS from the other closely related species. In accordance with the International Code of Nomenclature for Algae, Fungi and Plants, we propose the name of the new species to be Scytonema pachmarhiense.

The influence of sigma factors and ribosomal recognition elements on heterologous expression of cyanobacterial gene clusters in Escherichia coli

Abstract
Cyanobacterial natural products offer new possibilities for drugs and lead compounds but many factors can inhibit the production of sufficient yields for pharmaceutical processes. While Escherichia coli and Streptomyces sp. have been used as heterologous expression hosts to produce cyanobacterial natural products, they have not met with resounding success largely due to their inability to recognize cyanobacterial promoter regions. Recent work has shown that the filamentous freshwater cyanobacterium Anabaena sp. strain PCC 7120 recognizes various cyanobacterial promoter regions and can produce lyngbyatoxin A from the native promoter. Introduction of Anabaena sigma factors into E. coli might allow the native transcriptional machinery to recognize cyanobacterial promoters. Here, all 12 Anabaena sigma factors were expressed in E. coli and subsets were found to initiate transcription from several cyanobacterial promoters based on transcriptional fusions to the chloramphenicol acetyltransferase (CAT) reporter. Expression of individual Anabaena sigma factors in E. coli did not result in lyngbyatoxin A production from its native cyanobacterial gene cluster, possibly hindered by deficiencies in recognition of cyanobacterial ribosomal binding sites by native E. coli translational machinery. This represents an important step toward engineering E. coli into a general heterologous expression host for cyanobacterial biosynthetic gene cluster expression.

The unexpected diversity of microbial communities associated with black corals revealed by high-throughput Illumina sequencing

Abstract
The microbes associated with black corals remain poorly studied. The present study is the first attempt to investigate microbial community structure in the black corals Antipathes ceylonensis and A. dichotoma from the South China Sea by using high-throughput Illumina sequencing. A total of 52 bacterial and 3 archaeal phyla were recovered in this study, suggesting the black corals harboured highly diverse microbial communities. Among the 55 microbial phyla, Proteobacteria, Firmicutes, Bacteroidetes, Chloroflexi, Acidobacteria and Actinobacteria dominated in the two black corals from the South China Sea. Although most of the microbial phyla recovered from the two black corals have been reported in previous studies on coral-associated microbes, eight bacterial phyla including Synergistetes, Thermi, AncK6, GNO2, NKB19, NC10, WWE1 and GAL15, and the archaeal phylum Parvarchaeota are reported for the first time from corals in this study, which expands our knowledge about the diversity of coral-associated microbes. The comparison of microbial communities in the different black coral species indicated that A. ceylonensis harboured few abundant bacterial genera such as Citrobacter and Pseudomonas, whereas a high diversity of rare bacterial genera (<1% abundance), such as Winogradskyella and Rubricoccus, was detected only in A. dichotoma. These results suggested that the microbial community in black corals exhibited species-specific variation.

Detection of VBNC Vibrio cholerae by RT-Real Time PCR based on differential gene expression analysis

Abstract
The recognition of the viable but non-culturable (VBNC) state of pathogenic bacteria has brought with it many questions to answer related to the need to detect and quantify viable bacteria in the environment in an accurate way. To assess viability of Vibrio cholerae, we developed a RT-Real Time PCR technique based on differential expression analysis from mRNA deep sequencing data. We compared two induction conditions to achieve the VBNC state: a bacterial suspension induced by artificial seawater at 4°C, and the addition of 3',5'-cyclic diguanylic acid. The evaluation of the up-regulated genes in the induced bacterial samples was compared with a fresh culture in the mid-exponential phase. The data analysis was performed with the NOISeq R-package and revealed 17 up-regulated genes for induction condition I and 22 up-regulated genes for induction condition II. Only one region was found to be up-regulated for both induction conditions. The VCA0656 gene related to the aminoimidazole riboside kinase protein was detected as the most up-regulated region and used as a genetic marker to precisely detect the VBNC state in combination with the RT-Real Time PCR technique. This approach describes a novel method to differentiate the VBNC state of V. cholerae in water samples.

Molecular diversity of fungal inhibitor cystine knot peptides evolved by domain repeat and fusion

Abstract
Peptides with the inhibitor cystine knot (ICK) motif are extensively present in animals and plants where they exert a diversity of biological functions. However, few studies have been undertaken on this class of peptides in fungi. In this work, we identify a total of 386 fungal ICK peptides and proteins containing this motif by computational data mining of fungal genome databases, which exhibit 14 different exon–intron structures. According to their domain architectures, these proteins are classified into three distinct structural types, including single domains, tandem repeat domains and fusion domains, in which six families belonging to single or tandem repeat domains show remarkable sequence similarity to those from animals and plants, suggesting their orthologous relationship. Extremely high molecular diversity in fungal ICKs might be attributable to different genetic mechanisms, such as gene/domain duplication and fusion. This work not only enlarges the number of ICK peptides in multicellular organisms, but also uncovers their complex evolutionary history in a specific lineage.

Effect of gpd box copy numbers in the gpdA promoter of Aspergillus nidulans on its transcription efficiency in Aspergillus niger

Abstract
In this study, we characterised PgpdA, PgpdA2B, PgpdA3B and PgpdA4B promoters, containing 1–4 copies of gpd box by modifying the gpdA promoter, and constructed pSZHGX-xynB expression vectors, which were introduced into Aspergillus niger CICC2462 through Agrobacterium-mediated transformation. Thus, An (PgpdA-xynB), An (PgpdA2B-xynB), An (PgpdA3B-xynB) and An (PgpdA4B-xynB) homozygous recombinant strains were obtained. The xylanase activity of homozygous recombinant strains was measured. The enzymatic activities of An (PgpdA-xynB), An (PgpdA2B-xynB), An (PgpdA3B-xynB) and An (PgpdA4B-xynB) peaked on the 7th day of fermentation, at 1578.67, 2333.88, 3588.38 and 3183.51 U·mL−1, respectively. SDS-PAGE and qRT-PCR analysis indicated that An (PgpdA3B-xynB), containing three copies of gpd box, demonstrated the highest levels of protein expression and transcription. These results suggested that the PgpdA3B promoter promotes highly efficient transcription and may serve as a strong constitutive promoter for efficient recombinant protein expression. Additionally, a number of constitutive promoters with various transcription efficiencies were identified for the metabolic engineering of A. niger. Accordingly, this study provides a new approach for obtaining promoters with different transcription efficiencies.

How persistent identifiers can save scientists time

Abstract
Research information is useful only if it can be shared—with other researchers, with research organizations (institutions, laboratories, funders and others), and with the wider community. In our digital age, that means sharing information between data systems. Persistent identifiers (PIDs) provide unique keys for people, places and things, which enables accurate mapping of information between these systems and supports the research process by facilitating search, discovery, recognition and collaboration. This article reviews the main PIDs used in research—digital object identifiers for publications, ORCID iDs for researchers, and a proposed new identifier for research organizations—as well as demonstrating how they are being used, and how, in combination, they can increase trust in research and the research infrastructure.

August iotaderma (#294)



Answers to CME examination



Fat reduction

Despite the favorable safety profile of liposuction, complications occur that need to be appropriately managed. In the second article in this continuing medical education series, the range of complications that may arise from liposuction are described, and the latest best practices to manage them are discussed. Specific technical strategies to prevent and minimize the risk of complications are also presented. Early recognition, accurate diagnosis, and proper clinical management can ensure an optimal outcome and patient satisfaction in individuals who are investing in fat reduction procedures.

July iotaderma (#293)



Answers to CME examination



Fat reduction

The advances in understanding the pathophysiology and anatomy of adipose tissue together with the emergence of technological innovations in procedures and devices for fat reduction have led to a dramatic rise in patient demand for this procedure. The objective of this continuing medical education series, which is intended for the novice or experienced dermatologist, is to provide an update of the pathophysiology and anatomic considerations of adipose tissue, and detail the liposuction procedure, from patient selection/management to the latest developments in liposuction devices.

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Table of Contents



Re-evaluating pyoderma gangrenosum patients for Behçet disease before initiating any invasive procedures is essential

To the Editor: I would kindly like to remind your readers that pyoderma gangrenosum–like lesions also occur in Behçet disease, as is stated in a comment on the study "Risk of developing pyoderma gangrenosum after procedures in patients with a known history of pyoderma gangrenosum—A retrospective analysis."1 As the authors mentioned, the pathergy phenomenon is associated with pyoderma gangrenosum, but pathergy can also be seen in other conditions such as Behçet disease.2 Although very rare, pyoderma gangrenosum–like lesions are one of the clinical manifestations of Behçet disease.

Response to “Comment on: ‘When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council’”

To the Editor: We thank Drs Daunton and Goulding1 for their interest in our article2 and for their comments. Naturally, we agree that "a holistic assessment is needed" in patients with atopic dermatitis, including consideration of "existent comorbidities," as stated in our article. It was beyond the scope of our recommendation to discuss in detail the many comorbidities of AD, including the associated neuropsychiatric issues that the International Eczema Council recently reviewed.3

Reply to: “Re-evaluating pyoderma gangrenosum patients for Behçet disease before initiating any invasive procedures is essential”

To the Editor: We would like to thank Dr Aksoy1 for drawing attention to the unique challenges facing patients with Behçet syndrome in the perioperative setting. Her comments serve as an important reminder for physicians who are translating research into the clinical setting: we must consider the representativeness of the study sample when we generalize results to other settings or populations. Our patients' disease was diagnosed by using the Su criteria, and the overall demographics of our cohort are consistent with the known epidemiology of the disease in the United States.

Bullous pemphigoid and diabetes mellitus: Are we missing the larger picture?

To the Editor: We read with interest the study by Benzaquen et al1 reporting an increased risk for development of bullous pemphigoid (BP) in patients who are receiving a dipeptidyl peptidase-4 inhibitor (DPP4i). Their findings are supported by previous studies showing a significant signal of increased risk for development of BP during exposure to a DPP4i in the European and French pharmacovigilance databases.1

Reply to: “Bullous pemphigoid and diabetes mellitus: Are we missing the larger picture?”

To the Editor: We read with interest the letter titled "Bullous pemphigoid and diabetes mellitus—are we missing the larger picture?" by Geller et al1 and have several comments. The authors discuss the claimed association between diabetes mellitus (DM) and bullous pemphigoid (BP) and speculate about its underlying mechanisms.

Comment on: “When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council”

To the Editor: We read with interest the recent expert panel recommendations by Simpson et al on when systemic therapies may be indicated in the management of atopic dermatitis (AD).1 The authors rightly highlight the importance of identifying and addressing potential biologic exacerbating factors such as infection or contact allergy, as well as the role of patient education in improving adherence to topical therapy. However, we believe that the recommendations offered are narrow in scope. AD, like so many other chronic skin diseases, is a condition in which a holistic biopsychosocial approach must be used to allow the clinician to fully understand the patient, so as to optimize treatment outcomes and patient well-being.

Introducing a New Section: SoMe and Behavioral Science

Everywhere we look lately, it seems people are accessing social media on one device or another, excitedly adopting the newest apps to remain connected. I've written about social media in our Journal, most recently in the context of stress factors. In the past two years, we've seen an increased volume of related submissions in which aesthetic surgeons evaluate return on investment, which apps are most reliable, primers for starting out, how residents engage Instagram, and the top 100 Twitter gurus to follow.1–6

How to Objectively Evaluate Nodule Complications and Volume Changes After Fat Grafting in Breast Augmentation

We have read with great interest the article entitled "Does Stromal Vascular Fraction Ensure a Higher Survival in Autologous Fat Grafting for Breast Augmentation? A Volumetric Study Using 3-Dimensional Laser Scanning" by Dr Chiu in the Aesthetic Surgery Journal.1 In this article, the author conducted a comparative study between patients who underwent fat grafting with stromal vascular fraction (SVF) and those without and found that there was no statistically significant difference on the survival rate of fat tissue, assessed by 3-dimensional (3D) laser imaging. Inspired by the author, we would like to express our opinion on the complications and volume assessment in breast augmentation with fat grafting.

Response to “How to Objectively Evaluate Nodule Complications and Volume Changes After Fat Grafting in Breast Augmentation”

We would like to thank Dr Luan and colleagues for the comments1 regarding our recent article entitled "Does Stromal Vascular Fraction (SVF) Ensure a Higher Survival in Autologous Fat Grafting for Breast Augmentation? A Volumetric Study Using 3-Dimensional Laser Scanning."2

Energy shifts induce membrane sequestration of DraG in Rhodospirillum rubrum independent of the ammonium transporters and diazotrophic conditions

Abstract
Metabolic regulation of Rhodospirillum rubrum nitrogenase is mediated at the post- translational level by the enzymes DraT and DraG when subjected to changes in nitrogen or energy status. DraT is activated during switch-off whileDraG is inactivated by reversible membrane association. We confirm here that the ammonium transporter, AmtB1, rather than its paralog AmtB2, is required for ammonium induced switch off. Amongst several substitutions at the N100 position in DraG, only N100K, failed to locate to the membrane following ammonium shock, suggesting loss of interaction through charge repulsion. When switch off was induced by lowering energy levels, either by darkness during photosynthetic growth or oxygen depletion under respiratory conditions, reversible membrane sequestration of DraG was independent of AmtB proteins and occurred even under non-diazotrophic conditions. We propose that under these conditions, changes in redox status or possibly membrane potential induce interactions between DraG and another membrane protein in response to the energy status.

Co-harboring of cephalosporin (bla)/colistin (mcr) resistance genes among Enterobacteriaceae from flies in Thailand

Abstract
The spreading of antimicrobial-resistant Enterobacteriaceae, especially those co-harboring plasmid-mediated cephalosporin (bla) and colistin (mcr) resistance genes, is becoming increasingly problematic. As a vector, flies carry antimicrobial-resistant bacteria (ARB) into human and livestock habitats. To investigate ARB in flies, we collected 235 flies from 27 sites (18 urban areas, five pig farms, and four chicken farms) in Thailand during 2013–2015. Cefotaxime-resistant Enterobacteriaceae (CtxRE) and bla-positive CtxRE were isolated from 70 (29.8%) and 48 (20.4%) flies, respectively. In 93 bla-positive CtxRE isolates that included Escherichia coli, Enterobacter spp., and Klebsiella pneumoniae from 48 flies, the most frequent bla gene was TEM (n = 62), followed by CTX-M-55 (n = 31), CTX-M-14 (n = 26), CMY-2 (n = 24), and SHV (n = 10), and 58 isolates harbored multiple types of these genes. In addition, we detected the mcr-1 (n = 1) and mcr-3 (n = 19) genes in bla-positive CtxRE isolates from 16 flies. In conjugation experiments, 10 mcr-3- and bla-positive isolates exhibited co-transfer of mcr-3 and blaTEM-1 genes. These results suggest that a relatively high proportion of flies in Thailand carries cephalosporin-resistant Enterobacteriaceae harboring co-transmissible cephalosporin and colistin resistance genes.

Relationship of diversity and the secondary structure in 16S-23S rDNA internal transcribed spacer: a case in Vibrio parahaemolyticus

Abstract
The 16S-23S rDNA internal transcribed spacer (ITS) sequence, located in the rrn operon, has been analyzed and evaluated for use in phylogenetic analysis and the detection target of bacteria. The ITS region displays a high level of diversity, being present in multiple copies and displaying variability in both length and sequence, and it carries more phylogenetic information than 16S rDNA. However, appropriately identifying ITS regions to use in analyses is challenging. To solve this problem, we analyzed the ITS regions in Vibrio parahaemolyticus and predicted the secondary structure of each analogous rrn transcript. The genomic DNA of V. parahaemolyticus contains approximately 8–14 rrns, making it more complex than the sequences of most other bacterial species. We analyzed 216 ITSs, of which 206 ITSs come from 18 complete genomes and 10 ITSs were identified in the present study. The subunits of each ITS were distinguished by their predicted secondary structures. We propose a refined backbone model of the V. parahaemolyticus ITS that can be applied to the sequences of other bacteria. The backbone includes C, V, tDNA, and linker blocks. These blocks, which may represent true functional units, may be used as potential targets for phylogenetic analysis or molecular detection.

Characterization of two glycosyl hydrolases, putative prophage endolysins, that target Clostridium perfringens

Abstract
Clostridium perfringens, a spore-forming anaerobic bacterium, causes food poisoning and gas gangrene in humans, and is an agent of necrotizing enteritis in poultry, swine and cattle. Endolysins are peptidoglycan hydrolases from bacteriophage that degrade the bacterial host cell wall causing lysis and thus harbor antimicrobial therapy potential. The genes for the PlyCP10 and PlyCP41 endolysins were found in prophage regions of the genomes from Clostridium perfringens strains Cp10 and Cp41, respectively. The gene for PlyCP10 encodes a protein of 351 amino acids, while the gene for PlyCP41 encodes a protein of 335 amino acids. Both proteins harbor predicted glycosyl hydrolase domains. Recombinant PlyCP10 and PlyCP41 were expressed in E. coli with C-terminal His-tags, purified by nickel chromatography, and characterized in vitro. PlyCP10 activity was greatest at pH 6.0, and between 50–100 mM NaCl. PlyCP41 activity was greatest between pH 6.5 and 7.0, and at 50 mM NaCl, with retention of activity as high as 600 mM NaCl. PlyCP10 lost most of its activity above 42°C, whereas PlyCP41 survived at 50°C for 30 minutes and still retained > 60% activity. Both enzymes had lytic activity against 75 C. perfringens strains (isolates from poultry, swine and cattle) suggesting therapeutic potential.

Unraveling molecular targets of bisphenol A and S in the thyroid gland

Abstract

Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1.



We cannot infer by accepting testimony

Abstract

While we can judge and believe things by merely accepting testimony, we cannot make inferences by merely accepting testimony. A good theory of inference should explain this. The theories that are best suited to explain this fact seem to be theories that accept a so-called intuitional construal of Boghossian's Taking Condition.



Species-specific means and within-species variance in glucocorticoid hormones and speciation rates in birds

Abstract
At macroevolutionary scales, stress physiology may have consequences for species diversification and subspecies richness. Populations that exploit new resources or undergo range expansion should cope with new environmental challenges, which could favour higher mean stress responses. Within-species variation in the stress response may also play a role in mediating the speciation process: in species with broad variation, there will always be some individuals that can tolerate an unpredictable environment, whereas in species with narrow variation there will be fewer individuals that are able to thrive in a new ecological niche. We tested for the evolutionary relationship between stress response, speciation rate and subspecies richness in birds by relying on the HormoneBase repository, from which we calculated within- and among-species variation in baseline and stress-induced corticosterone levels. To estimate speciation rates, we applied Bayesian analysis of macroevolutionary mixtures that can account for variation in diversification rate among clades and through time. Contrary to our predictions, lineages with higher diversification rates were not characterized by higher baseline or stress-induceved levels of corticosterone either at the tips or at the deeper nodes of the phylogeny. We also found no association between mean hormone levels and subspecies richness. Within-species variance in corticosterone levels showed close to zero repeatability, thus it is highly unlikely that this is a species-specific trait that influences diversification rates. These results imply that stress physiology may play a minor, if any, role in determining speciation rates in birds.

Metrics of the Aesthetically Perfect Breast

Abstract

Breast surgery has long been viewed as an art more than a science. However, defining and objectively measuring the ideal breast morphology and aesthetic proportions are fundamental for surgical planning and to setting the goals of surgery as well as to evaluate surgical outcomes. Despite the fact that much has been written about aesthetic and reconstructive breast surgery, there is still no real consensus about what the attributes are of an ideal breast. Moreover, there are in fact no objective standard measurement systems and guidelines to describe ideal or even normal breast shape. Though there is great variability in the perception of beauty among patients and surgeons alike due to many factors among which are age, sex, and sociocultural background, there is common agreement that beauty is a universal phenomenon that has a universal standard present across all civilizations and centuries, and that perceived beauty is enhanced and optimal aesthetics are achieved when proper measurements are made and anthropometric proportions as well as attractive harmonious ratios are respected. The current review is an attempt to summarize the most relevant information available trying to introduce some harmony in our perception of aesthetic ideals of breast surgery.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.



Combining plasma-based biosources to predict treatment response in NSCLC patients



Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study

Abstract
Background
Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies.
Patients and methods
Eligible patients (Eastern Cooperative Oncology Group performance status 0–1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1:1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) by central review. Secondary endpoints included objective tumor response and disease control by central review.
Results
From October 2014 – January 2016, 768 patients were randomized; 765 were treated (nintedanib n=384; placebo n=381). Median follow-up was 13.4 months (interquartile range, 11.1–15.7). OS was not improved (median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.86 to 1.19; P = 0.8659). There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR, 0.58; 95% CI, 0.49 to 0.69; P<0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%).
Conclusions
The study failed to meet both co-primary endpoints. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated.This trial is registered at ClinicalTrials.gov: NCT02149108.

Original article: Training and validation of a novel 4-miRNA ratio model (MiCaP) for prediction of post-operative outcome in prostate cancer patients

Abstract
Background
New molecular biomarkers for prostate cancer (PC) prognosis are urgently needed. Ratio-based models are attractive, as they require no additional normalization. Here, we train and independently validate a novel 4-miRNA prognostic ratio model for PC.
Patients and methods
By genome-wide miRNA expression profiling of PC tissue samples from 123 men who underwent radical prostatectomy (RP) (PCA123, training cohort), we identified six top candidate prognostic miRNAs and systematically tested their ability to predict post-operative biochemical recurrence (BCR). The best miRNA-based prognostic ratio model (MiCaP) was validated in two independent cohorts (PCA352 and PCA476) including >800 RP patients in total. Clinical endpoints were BCR and prostate cancer-specific survival (CSS). The prognostic potential of MiCaP was assessed by univariate and multivariate Cox-regression analyses and Kaplan-Meier analyses.
Results
We identified a 4-miRNA ratio model, MiCaP (miR-23a-3p×miR-10b-5p)/(miR-133a×miR-374b-5p), that predicted time to BCR independently of routine clinicopathological variables in the training cohort (PCA123) and was successfully validated in two independent RP cohorts. In addition, MiCaP was a significant predictor of CSS in univariate analysis (HR 3·35 [95% CI 1·34 – 8·35], P=0·0096) and in multivariate analysis (HR 2·43 [95% CI 1·45 – 4·07], P=0·0210). As proof-of-principle, we also analyzed MiCaP in plasma samples from 111 RP patients. A high MiCaP score in plasma was significantly associated with BCR (P=0·0036, Kaplan-Meier analysis). Limitations include low mortality rates (CSS: 5.4%).
Conclusions
We identified a novel 4-miRNA ratio model (MiCaP) with significant independent prognostic value in three RP cohorts, indicating promising potential to improve PC risk stratification.

Correlation of extent of ALK FISH positivity and crizotinib efficacy in three prospective studies of ALK-positive patients with non-small cell lung cancer

Abstract
Background
In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)—particularly near the cutoff defining positive status—and clinical outcomes have been limited by small sample sizes.
Patients and methods
Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cutoff of ≥ 15% ALK-positive cells. Logistic regression and proportional hazards regression analyses were used to explore the association of percent ALK-positive cells with objective response and progression-free survival (PFS), respectively.
Results
Of 11 081 screened patients, 1958 (18%) were ALK-positive, 7512 (68%) were ALK-negative, and 1540 (14%) were uninformative. Median percentage of ALK-positive cells was 58% in ALK-positive patients and 2% in ALK-negative patients. Of ALK-positive patients, 5% had 15–19% ALK-positive cells; of ALK-negative patients, 2% had 10 − 14% ALK-positive cells. Objective response rate for ALK-positive, crizotinib-treated patients with ≥20% ALK-positive cells was 56% (n=700/1246), 55% (n=725/1312) for those with ≥15% ALK-positive cells, and 38% for those with 15–19% ALK-positive cells (n=25/66). As a continuous variable, higher percentages of ALK-positive cells were estimated to be associated with larger differences in objective response and PFS between crizotinib and chemotherapy; however, tests for interaction between treatment and percentage of ALK-positive cells were not significant (objective response, P=0.054; PFS, P=0.17).
Conclusions
Patients with ALK-positive NSCLC benefit from treatment with crizotinib across the full range of percentage of ALK-positive cells, supporting the clinical utility of the 15% cutoff. The small number of patients with scores near the cutoff warrant additional study given the potential for misclassification of ALK status due to technical or biologic reasons.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Abstract
Background
Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.
Patients and Methods
Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg IV 3 weekly for 1 year) or standard observation. The primary endpoint was detection of an 8% difference in 5 year overall survival (OS) rate; secondary endpoints included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers.
Results
1343 patients recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4 years median follow-up, 515 (38%) patients had died (254 [38%] bevacizumab; 261 [39%] observation); 707 (53%) patients had disease recurrence (336 [50%] bevacizumab, 371 [55%] observation). OS at 5 years was 64% for both groups (Hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.82-1.16, p=0.78). At 5 years, 51% were disease-free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, p=0.03), 58% were distant metastasis-free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, p=0.25). 44% of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild type patients (p=0.06). BRAF mutation positivity trended towards better OS with bevacizumab (p=0.21).
Conclusions
Adjuvant bevacizumab after resection of high risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab.

Value of bone marrow biopsy in Hodgkin lymphoma patients staged by FDG PET: Results from the German Hodgkin Study Group trials HD16, HD17, and HD18

Abstract
Background
Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning is performed during staging.
Patients and methods
Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not.
Results
Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% (95% confidence interval: 99.2-100%) with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% confidence interval: 75.1-99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy.
Conclusions
As compared to BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol.
Registered trials
The trials included in this analysis were registered at ClinicalTrials.gov: HD16 - NCT00736320, HD17 - NCT01356680, HD18 - NCT00515554.

The legacy of Thomas Tursz: building a leading comprehensive cancer center in Europe



Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer

Abstract
Background
Measuring cell-free (cf)DNA in blood and tissues holds significant potential as a minimally invasive method for disease monitoring in cancer. Cancers arising in the oropharynx and causally linked to human papillomavirus (HPV) represent an ideal model in which to interrogate these methods.
Patients and methods
We designed an ultrasensitive and quantitative droplet digital (dd)PCR assay to detect the five dominant high-risk HPV subtypes linked to oropharyngeal cancer (OPC). We enrolled a pilot observational cohort of 22 patients with advanced HPV+ OPC to evaluate the clinical utility of our assay and explore its predictive and prognostic potential.
Results
Total tumor burden (TTB) strongly correlated with HPV cfDNA levels (R = 0.91, P = 2.3 x 10−6) at this cohort size, and in most cases more distant anatomic disease locations predicted increasing HPV cfDNA levels. All participants demonstrated a corresponding change in their HPV cfDNA levels at a median of 16 days (range: 12-38) prior to restaging scans confirming treatment response or progression. Patients with locoregional disease in the head and neck or pulmonary-only metastases had worse outcomes (P = 0.01). Both TTB and median plasma HPV cfDNA levels negatively correlated with survival (R = -0.65, P = 0.01; R = -0.48, P = 0.05, respectively).
Conclusion(s)
Plasma HPV cfDNA monitoring recapitulates fluctuations in disease status. While blood-based HPV DNA monitoring does not currently have a role in managing HPV+ OPC, these data speak to their broad clinical potential in an era of precision medicine.

Addressing the quality of life needs of older patients with cancer: A SIOG consensus paper and practical guide

Abstract
Around 60% of people living with cancer are aged 65 years or older. Older cancer patients face a unique set of age-associated changes, comorbidities, and circumstances that impact on their quality of life (QoL) in ways that are different to those affecting younger patients. A Task Force of the International Society of Geriatric Oncology (SIOG) recommends and encourages all healthcare professionals involved in cancer care to place greater focus on the QoL of older people living with cancer. This paper summarizes current thinking on the key issues of importance to addressing QoL needs of older cancer patients and makes a series of recommendations, together with practical guidance.

Reply to the Letter to the Editor "Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies" by X. Dong, G. Ma and F. Chen



Now the dust has settled over immune checkpoint blockade in metastatic prostate cancer



Reply to the Letter to the Editor "What type of man against machine?" by H. Smith



Patients with urticaria are at a higher risk of anaphylaxis: A nationwide population‐based retrospective cohort study in Taiwan

The Journal of Dermatology, EarlyView.


Coexistence of X‐linked ichthyosis and Nagashima‐type palmoplantar keratosis: A case report

The Journal of Dermatology, EarlyView.


Serum interleukin‐34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease

The Journal of Dermatology, EarlyView.


Effects of tumor necrosis factor‐α, interleukin‐23 and interleukin‐17A inhibitors on bodyweight and body mass index in patients with psoriasis

The Journal of Dermatology, EarlyView.


Corrigendum to ``Patient-rated long-term results after complete denervation of the wrist'' [Journal of Plastic, Reconstructive & Aesthetic Surgery Volume 71 Issue 1 (2018) 57–61]

Publication date: Available online 12 July 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): T. Fuchsberger, P. Gonser, C.E. Boesch, F. Tonagel, T. Fischborn, H.E. Schaller, M. Haerle



Reduction of the DIEP flap donor site morbidity through a minimally invasive pedicle harvest with Jacob's ladder incisions

Publication date: June 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery, Volume 71, Issue 6

Author(s): Laurenz Weitgasser, Amro Amr, Franziska Leandra Reutzsch, Thomas Schoeller

Abstract

Despite the decrease of donor-site morbidity through the introduction of the deep inferior epigastric artery perforator (DIEP) flap as successor of the free transverse rectus abdominis (TRAM) flap, abdominal complications still occur. The etiology of lower abdominal bulging following breast reconstruction with the DIEP flap is still under debate. Most studies estimate the incidence for a postoperative lower abdominal bulging to be between 0.7% and 5%. However, a higher number of undetected and unreported cases is not unusual. The authors present their approach to further reduce the donor site morbidity of the DIEP flap pedicle harvest through minimally invasive Jacob's ladder incisions. The authors aim was to assess the technical feasibility of this minimally invasive pedicle harvest and discuss advantages and disadvantages compared to endoscopic or robotic assisted techniques.



Biomonitoring of Benzene and Effect of Wearing Respirators during an Oil Spill Field Trial at Sea

Abstract
Objectives
The main aim of this study was to assess the biological uptake of benzene and polycyclic aromatic hydrocarbons (PAHs) for subjects exposed to fresh crude oil released at sea.
Methods:
The study included 22 subjects participating in an 'oil-on-water' field trial in the North Sea. Over 2 consecutive days, there were six releases with two different types of fresh crude oils. Exposed subjects (n = 17) were either located in small, open-air boats downwind and close to the released oil (<50 m) or on the main deck of two large vessels further from the released oil (100–200 m). Subjects assumed to be unexposed (n = 5) were located indoors on the command bridge of either vessel. Full-shift personal benzene exposure was monitored with passive thermal desorption tubes (ATD-tubes) packed with Tenax TA and subsequent gas chromatographic analysis. Urine samples were collected before and after work-shift on both days and analyzed for urinary markers of benzene [(S-phenylmercapturic acid (SPMA)] and PAHs [1-hydroxypyrene (1-OH)]. Information about the use of personal protective equipment, smoking habits, location, work tasks, and length of work-shift were recorded by a questionnaire.
Results
Subjects located in the small boats downwind and close to the released oil were exposed to relatively high concentrations of benzene (arithmetic mean = 0.2 ppm, range 0.002–1.5 ppm) compared to the occupational exposure limits (OELs) for 8 h (1 ppm) and 12 h (0.6 ppm). Although respirators were available to all exposed subjects, SPMA was detected in post-shift urine (0.5–3.3 µmol mol−1) of five exposed subjects reporting not wearing respirators, all located in the small boats downwind and close to the released oil. For exposed subjects wearing respirators (n = 12), the post-shift urinary SPMA was below the detection limit (0.8 µmol mol−1) even when the benzene exposure exceeded the OELs. Urinary levels of PAH were within the reference range of what is considered as background levels (<0.4 µmol mol−1).
Conclusions
During the initial stages of a bulk oil spill at sea, when the evaporation of benzene is at its highest, it is important to use appropriate respirators to prevent biological uptake of benzene.

Multigroup latent class model of musculoskeletal pain combinations in children/adolescents: identifying high-risk groups by gender and age

To investigate the combinations of Musculoskeletal pain (MSP) (neck, shoulder, upper and low back pain) among a sample of Iranian school children.

Medication-overuse headache: a widely recognized entity amidst ongoing debate

Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. The burden of disease on individuals and societies is significant due to h...

Chronic and intermittent administration of systemic nitroglycerin in the rat induces an increase in the gene expression of CGRP in central areas: potential contribution to pain processing

Calcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular system and it is likely related to migraine chronification. Here, we investigated the role of CG...

Feasibility of serum CGRP measurement as a biomarker of chronic migraine: a critical reappraisal

Calcitonin gene-related peptide (CGRP) has been reported as elevated in chronic migraine. We aimed to validate the role of interictal serum CGRP concentration in peripheral blood samples as a biomarker of chro...

Industrial water use, income, trade, and employment: environmental Kuznets curve evidence from 17 Taiwanese manufacturing industries

Abstract

This paper investigated the relationships between industrial water use, income, trade, and employment for 17 Taiwanese industries from 1998 to 2015. We explored cross-sectional dependent unit root, panel cointegration, and causality tests to estimate their long-term relationships and causal nexus. There existed long-term equilibrium relationships among the variables. The long-term elasticity estimates of industrial water use with respect to income, squared income, trade, and employment are 4.27, − 0.15, 0.22, and 0.92, respectively. The results do not confirm an inverted U-shaped environmental Kuznets curve. A unidirectional causal relationship is found between water use and income, and a bidirectional causal relationship is identified between water use and employment. Exports cause industrial water use. As expected, both employment and exports lead to income. Hence, policy makers should promote investment into water efficiency and water recycling. Various governments reward firms for water efficiency and lower consumption without negative long-term effects on economic growth.



Toward a standard ontology of surgical process models

Abstract

Purpose

The development of common ontologies has recently been identified as one of the key challenges in the emerging field of surgical data science (SDS). However, past and existing initiatives in the domain of surgery have mainly been focussing on individual groups and failed to achieve widespread international acceptance by the research community. To address this challenge, the authors of this paper launched a European initiative—OntoSPM Collaborative Action—with the goal of establishing a framework for joint development of ontologies in the field of SDS. This manuscript summarizes the goals and the current status of the international initiative.

Methods

A workshop was organized in 2016, gathering the main European research groups having experience in developing and using ontologies in this domain. It led to the conclusion that a common ontology for surgical process models (SPM) was absolutely needed, and that the existing OntoSPM ontology could provide a good starting point toward the collaborative design and promotion of common, standard ontologies on SPM.

Results

The workshop led to the OntoSPM Collaborative Action—launched in mid-2016—with the objective to develop, maintain and promote the use of common ontologies of SPM relevant to the whole domain of SDS. The fundamental concept, the architecture, the management and curation of the common ontology have been established, making it ready for wider public use.

Conclusion

The OntoSPM Collaborative Action has been in operation for 24 months, with a growing dedicated membership. Its main result is a modular ontology, undergoing constant updates and extensions, based on the experts' suggestions. It remains an open collaborative action, which always welcomes new contributors and applications.



On representationalism, common-factorism, and whether consciousness is here and now

Abstract

A strong form of representationalism says that every conscious property of every mental state can be identified with some part of the state's representational properties. A weaker representationalism says that some conscious property of some mental state can be identified with some part of the state's representational properties. David Papineau has recently argued that all such theories are incorrect since (a) they construe consciousness as consisting (partly or wholly) in "relations to propositions or other abstract objects outside space and time", whereas (b) consciousness is "concrete" and "here and now". Papineau defends instead a kind of "qualia theory" according to which all conscious properties are intrinsic non-relational properties of subjects. He argues that this theory bypasses the difficulties he identifies for representationalism. Similar worries about representationalism, and similar ideas to the effect that some qualia theory, adverbial theory, or sense-datum theory fares better with respect to these worries are relatively wide-spread. I argue that Papineau's theory does not bypass the difficulties he identifies for representationalism. In fact, Papineau's theory arguably has no advantage at all over representationalism with regard to these issues. The features that concern Papineau about representationalist views do not derive—or do not derive solely—from the representationalism of these views. They (also) derive from a common-factorism of these views. And this common-factorism is embraced by Papineau as well as by most theories of consciousness and perception.



Magnetic resonance imaging surrogates of molecular subgroups in atypical teratoid / rhabdoid tumor (ATRT)

Abstract
Background
Recently, three molecular subgroups of atypical teratoid/rhabdoid tumor (ATRT) were identified, but little is known on their clinical and magnetic resonance imaging (MRI) characteristics.
Methods
A total of 43 patients with known molecular subgroup status (ATRT-SHH n=17, ATRT-TYR n=16, ATRT-MYC n=10) were retrieved from the EU-RHAB registry and analyzed for clinical and MRI features.
Results
On MRI review, differences in preferential tumor location were confirmed, with ATRT-TYR being predominantly located infratentorially (p<.05). Peritumoral edema was more pronounced in ATRT-MYC, compared to ATRT-SHH (p<.05) and ATRT-TYR (p<.05). Conversely, peripheral tumor cysts were found more frequently in ATRT-SHH (71%) and ATRT-TYR (94%), as compared to ATRT-MYC (40%, p<.05). Contrast enhancement was absent in 29% of ATRT-SHH (0% of ATRT-TYR; 10% of ATRT-MYC; p<.05), and there was a trend towards strong contrast enhancement in ATRT-TYR and ATRT-MYC. We found the characteristic (band-like) enhancement in 28% of ATRT as well as restricted diffusion in the majority of tumors. A midline/off-midline location in the posterior fossa was also not subgroup-specific. Visible meningeal spread (M2) at diagnosis was rare throughout all subgroups.
Conclusions
These exploratory findings suggest that MRI features vary across the three molecular subgroups of ATRT. Within future prospective trials, MRI may aid diagnosis and treatment stratification.

Surgical treatment of periocular basal cell carcinomas with whole specimen intraoperative frozen section analysis: experiences and review of literature

Abstract

Background

Periocular skin tumors are difficult to treat because of the friability of the tissue and close relationship to adjacent, functional structures. After excision, direct reconstruction with alike tissue is desirable to prevent shrinkage and deformation. We analyzed whether a quick intraoperative pathology method using whole specimen bread loaf frozen section analysis delivers a sufficiently reliable result concerning completeness of the excision in periocular basal cell carcinoma (BCC).

Methods

This is a cohort study by case note review of 132 patients undergoing excision of periocular BCC between 1996 and 2012 at the Medical Centre Leeuwarden. Whole specimen intraoperative frozen section analysis (WIFSA) was performed and compared with final paraffin-embedded tissue sections. Sensitivity and specificity of WIFSA and 5-year recurrence rate were calculated.

Results

One hundred thirty-nine periocular BCCs were excised. Paraffin sections of primary excision showed clear margins in 90 cases and tumor-positive margins in 49 cases. In 87 of 90 excisions with clear margins, WIFSA showed clear margins as well (specificity 97%). In 48 of the 49 excisions with tumor-positive margins, WIFSA showed incomplete excision as well (sensitivity 98%). Recurrence rate was 3.6% (5/139), with average follow-up of 79 months.

Conclusions

This study indicates that WIFSA is an effective method for histological examination of the margins of surgically removed periocular BCCs, with high specificity and sensitivity. Recurrence rates are low.

Level of Evidence: Level II, diagnostic study.



Mobility of metal(loid)s at the sediment-water interface in two tourist port areas of the Gulf of Trieste (northern Adriatic Sea)

Abstract

One of the main environmental issues affecting coastal marine environments is the accumulation of contaminants in sediments and their potential mobility. In situ benthic chamber experiments were conducted at two tourist ports (marinas) located in the Gulf of Trieste, one in Slovenia and one in Italy. The aim was to understand if and where recycling at the sediment-water interface (SWI) may affect metal(loid)s. Short sediment cores were also collected near the chamber to investigate the solid (sediments) and dissolved phases (porewaters). Both diffusive and benthic fluxes were estimated to elucidate the release of metal(loid)s at the SWI. Total element concentrations and their labile fractions were determined in sediments to quantify their potential mobility. The total element contents were found to be two orders of magnitude higher in the Italian marina than in the Slovenian one, especially for Hg (up to 1000 mg kg−1), whereas the labile fraction was scarce or null. The opposite occurred in the Slovenian marina. Metal(loid)s in porewaters showed a clear diagenetic sequence and a close dependence upon the suboxic/anoxic conditions of sediments. The results suggest that although the sediments of the Italian marina exhibit the highest total metal(loid) concentration, these elements are scarcely remobilisable. Conversely, in the Slovenian marina, sediments seem to be comparatively more prone to release metal(loid)s at the SWI.