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Σάββατο 14 Ιουλίου 2018

Monitoring of methane emission from a landfill site in daily and hourly time scales using an automated gas sampling system

Abstract

Landfill sites are significant sources of methane gas globally. Understanding the temporal variabilities of methane emissions from landfill sites is necessary for estimating such emissions. In this study, an automated monitoring system was used to monitor methane emission flux and concentration on daily and hourly time scales at a landfill site. Measured methane emission fluxes were almost negligible in the studied area. However, methane concentration at landfill surface at nighttime was significantly higher than those in the daytime, which demonstrates the importance of investigating methane emissions at an hourly time scale, including during nighttime. The daily and hourly variations in methane concentration were well correlated with either soil temperature or volumetric water content near the surface. The obtained relations indicate that the automated monitoring system measurements can facilitate a more comprehensive understanding of the methane emission mechanisms at different time scales.



Polarized Secretion of Extracellular Vesicles by Mammary Epithelia

Abstract

Extracellular vesicles (EVs) are secreted by many cell types and are increasingly investigated for their role in human diseases including cancer. Here we focus on the secretion and potential physiological function of non-pathological EVs secreted by polarized normal mammary epithelial cells. Using a transwell system to allow formation of epithelial polarity and EV collection from the apical versus basolateral compartments, we found that impaired secretion of EVs by knockdown of RAB27A or RAB27B suppressed the establishment of mammary epithelial polarity, and that addition of apical but not basolateral EVs suppressed epithelial polarity in a dose-dependent manner. This suggests that apical EV secretion contributes to epithelial polarity, and a possible mechanism is through removal of certain intracellular molecules. In contrast, basolateral but not apical EVs promoted migration of mammary epithelial cells in a motility assay. The protein contents of apical and basolateral EVs from MCF10A and primary human mammary epithelial cells were determined by mass spectrometry proteomic analysis, identifying apical-EV-enriched and basolateral-EV-enriched proteins that may contribute to different physiological functions. Most of these proteins differentially secreted by normal mammary epithelial cells through polarized EV release no longer showed polarized secretion in MCF10A-derived transformed epithelial cells. Our results suggest an essential role of EV secretion in normal mammary epithelial polarization and distinct protein contents and functions in apical versus basolateral EVs secreted by polarized mammary epithelia.



Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats

Abstract

Breast development occurs through well-defined stages representing 'windows of susceptibility' to adverse environmental exposures that potentially modify breast cancer risk. Systematic characterization of morphology and transcriptome during normal breast development lays the foundation of our understanding of cancer etiology. We examined mammary glands in female Sprague Dawley rats across six developmental stages – pre-pubertal, peri-pubertal, pubertal, lactation, adult parous and adult nulliparous. We investigated histology by Hematoxylin and Eosin and Mallory's Trichrome stain, proliferative and apoptotic rate by immunohistochemistry and whole-transcriptome by microarrays. We identified differentially expressed genes between adjacent developmental stages by linear models, underlying pathways by gene ontology analysis and gene networks and hubs active across developmental stages by coexpression network analysis. Mammary gland development was associated with large-scale changes in the transcriptome; particularly from pre-pubertal to peri-pubertal period and the lactation period were characterized by distinct patterns of gene expression with unique biological functions such as immune processes during pre-pubertal development and cholesterol biosynthesis during lactation. These changes were reflective of the shift in mammary gland histology, from a rudimentary organ during early stages to a secretory organ during lactation followed by regression with age. Hub genes within mammary gene networks included metabolic genes such as Pparg during the pre-pubertal stage and tight junction-related genes claudins and occludins in lactating mammary glands. Transcriptome profile paired with histology enhanced our understanding of mammary development, which is fundamental in understanding the etiologic mechanism of breast cancer, especially pertaining to windows of susceptibility to environmental exposures that may alter breast cancer risk.



Genetic polymorphism in Hsp90AA1 gene is associated with the thermotolerance in Chinese Holstein cows

Abstract

The heat shock protein 90 (Hsp90) is a copious and ubiquitous molecular chaperone which plays an essential role in many cellular biological processes. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the Hsp90AA1 gene and to determine their association with heat stress traits in Chinese Holstein cattle breed. Direct sequencing was used to identify new SNPs. Luciferase reporter assay methods were used to assess g.− 87G > C and g.4172A > G loci in the promoter activity and 3′-UTR, respectively. Quantitative real-time PCR was utilized to quantify the gene expression profile. Five SNPs were identified in 130 multiparous lactating cows: one SNP in the promoter, three SNPs in the coding region, and one in 3′-UTR were novel and reported for the first time in this study. As a result of promoter assay using dual luciferase assay system, the genotype CC showed the highest transcription activity region (13.67 ± 0.578) compared to the wild-type GG (3.24 ± 0.103). On the other hand, the result revealed that one of the selected microRNAs (dme-miR-2279-5p) was found to interact with the Hsp90AA1 3′-UTR sequence and to suppress the reporter activity markedly in the presence of the allele G (2.480 ± 0.136). The expression of Hsp90AA1 in cow bearing mutant allele C was higher (4.18 ± 0.928) than cows bearing wild-type allele G (1.008 ± 0.0.129) in stress season. In summary, there was an association between genetic variations in the Hsp90AA1 and thermoresistance. This association could be used as a marker in genetic selection for heat tolerance in Chinese Holstein cattle breeds.



HSP60 expression profile under different extreme temperature stress in albino northern snakehead, Channa argus

Abstract

The great albino northern snakehead, Channa argus, is one of the most important economical fish in China. In the present study, cDNA encoding heat shock protein 60 (HSP60) was cloned and characterized. The cDNA was 2462 bp, containing an open reading frame (ORF) encoding a 575-amino-acids polypeptide of 61.10 kDa (theoretical isoelectric point [pI]: 5.66). BLAST analysis showed that AcaHSP60 was highly similar with other HSP60s, and three conserved amino acid blocks and characteristic motifs or domains defined as HSP60 protein family signatures. Genomic DNA analysis showed that AcaHSP60 had ten exons in the coding region (from 94 to 336 bp). Changes in AcaHSP60 gene expression profiles in albino C. argus experimentally exposed to different temperature stress (8.5, 26, and 37 °C) was investigated. Quantitative real-time PCR and western blot analysis revealed that tissue-specific AcaHSP60 expressions were in the spleen, muscle, liver, kidney, heart and brain. Expression was highly significantly stimulated after heat shock (37 °C), but showed no significant differences after cold treatment (8.5 °C) except in the brain. In summary, these results showed that AcaHSP60 was significantly tissue specific and indicate that AcaHSP60 expression might be sensitive to thermal resistance in albino C. argus.



HO-1 dependent antioxidant effects of ethyl acetate fraction from Physalis alkekengi fruit ameliorates scopolamine-induced cognitive impairments

Abstract

Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells. The potent EA fraction then investigated and confirmed for its involvement of HO-1 pathway using hemin (HO-1 inducer) and ZnPP (HO-1 inhibitor) through Western blotting, DCFH-DA, and/or Griess assay. The involvements of PI3K/Akt, MEK, and p38 MAPK also investigated. Furthermore, we applied EA fraction to the animals at 100 and 200 mg/kg doses to check if the extract could improve scopolamine-induced memory deficits in passive avoidance and elevated plus maze tests. Our results demonstrated that the fractions from PAF significantly inhibited the generation of intracellular reactive oxygen species (ROS) induced by LPS in concentration-dependent manners. In comparison to other fractions, the EA fraction exhibited potent effect in suppressing intracellular ROS generation. Besides, EA fraction also induced the expression of HO-1 in time- and concentration-dependent manners. ZnPP significantly reversed the suppressive effect of EA fraction on LPS-induced ROS generation and NO production, which confirm the involvement of HO-1 signaling in EA-fraction-mediated antioxidant activities. Consistently, blocking of PI3K/Akt, MEK, and p38 MAPK pathways by PAF-EA suppressed the production of intracellular ROS, indicating their potential participation. In addition, one of the major constituents of EA fraction, luteolin-7-O-β-D-glucoside, also demonstrated HO-1-dependent antioxidant effects in BV2 cells. Further, the EA fraction significantly (p < 0.05) improves scopolamine-induced memory deficits in mice. Taken together, our findings highlight the antioxidant effects of EA fraction of PAF which may be beneficial in treatment of different neurodegenerative diseases associated with free radicals.



Vitamin C and sodium bicarbonate enhance the antioxidant ability of H9C2 cells and induce HSPs to relieve heat stress

Abstract

Heat stress is exacerbated by global warming and affects human and animal health, leading to heart damage caused by imbalances in reactive oxygen species (ROS) and the antioxidant system, acid-base chemistry, electrolytes and respiratory alkalosis. Vitamin C scavenges excess ROS, and sodium bicarbonate maintains acid-base and electrolyte balance, and alleviates respiratory alkalosis. Herein, we explored the ability of vitamin C alone and in combination with equimolar sodium bicarbonate (Vitamin C-Na) to stimulate endogenous antioxidants and heat shock proteins (HSPs) to relieve heat stress in H9C2 cells. Control, vitamin C (20 μg/ml vitamin C for 16 h) and vitamin C-Na (20 μg/ml vitamin C-Na for 16 h) groups were heat-stressed for 1, 3 or 5 h. Granular and vacuolar degeneration, karyopyknosis and damage to nuclei and mitochondria were clearly reduced in treatment groups, as were apoptosis, lactate dehydrogenase activity and ROS and malondialdehyde levels, while superoxide dismutase activity was increased. Additionally, CRYAB, Hsp27, Hsp60 and Hsp70 mRNA levels were upregulated at 3 h (p < 0.01), and protein levels were increased for CRYAB at 0 h (p < 0.05) and 1 h (p < 0.01), and for Hsp70 at 3 and 5 h (p < 0.01). Thus, pre-treatment with vitamin C or vitamin C-Na might protect H9C2 cells against heat damage by enhancing the antioxidant ability and upregulating CRYAB and Hsp70.



Pre-protective effects of dietary chitosan supplementation against oxidative stress induced by diquat in weaned piglets

Abstract

The protective effects of chitosan (CS) supplementations on oxidative stress induced by diquat in weaned piglets were investigated. A total of 36 crossbreed piglets with an average live body weight (BW) of 8.80 ± 0.53 kg were weaned at 28 ± 2 days and randomly divided into six dietary treatments (n = 6): control (basal diet), negative control (10 mg diquat/kg BW injected to piglets fed with basal diet), and basal diet treatments containing either 250, 500, 1000, or 2000 mg/kg of CS administered to piglets injected with 10 mg diquat/kg BW. The experiment conducted for 21 days which consisted of pre-starter period (14 days) and starter period (7 days). BW, feed intake, and fecal consistency were monitored. Blood samples were collected to determine antioxidative and immune parameters. CS supplementation improved the growth performance and decreased fecal score of piglets from days 1 to 14. Diquat also induced oxidative stress and inflammatory responses by decreasing the activities of antioxidant and regulating cytokines. But dietary CS alleviated these negative effects induced by diquat that showed decreasing serum concentrations of pro-inflammatory cytokines but increasing activities of antioxidant enzymes and anti-inflammatory cytokines. Results indicated that CS attenuated the oxidative stress of piglets caused by diquat injection.



DNA methylation rather than single nucleotide polymorphisms regulates the production of an aberrant splice variant of IL6R in mastitic cows

Abstract

Interleukin-6 receptor-alpha (IL6R) interacts with IL6 and forms a ligand–receptor complex, which can stimulate various cellular responses, such as cell proliferation, cell differentiation, and activation of inflammatory processes. Both genetic mutation and epigenetic modification regulate gene transcription. We identified a novel splice variant of bovine IL6R, designated as IL6R-TV, which is characterized by the skipping of exon 2 of the NCBI-referenced IL6R gene (IL6R-reference). The expression levels of IL6R-TV and IL6R-reference transcripts were lower in normal mammary gland tissues. These transcripts play a potential role during inflammatory infection. We also detected two putative functional SNPs (g.19711 T > C and g.19731 G > C) located within the upstream 100 bp of exon 2. These SNPs formed two haplotypes (T-G and C-C). Two mutant pSPL3 exon-trapping plasmids (pSPL3-T-G and pSPL3-C-C) were transferred into the bovine mammary epithelial cells (MAC-T) and human embryonic kidney 293 T cells (HEK293T) to investigate the relationship between the two SNPs and the aberrant splicing of IL6R. DNA methylation levels of the alternatively spliced exon in normal and mastitis-infected mammary gland tissues were quantified through nested bisulfate sequencing PCR (BSP) and cloning sequencing. We found that DNA methylation regulated IL6R transcription. The DNA methylation level was high in mastitis-infected mammary gland tissues and stimulated IL6R expression, thereby promoting the inclusion of the alternatively spliced exon. The upregulated expression of the two transcripts was due to DNA methylation modification rather than genetic mutations.



Correction to: Structural and functional aspects of the interaction partners of the small heat-shock protein in Synechocystis

Table 1 in the original publication has been corrected.



Heterologous expression of Oenococcus oeni sHSP20 confers temperature stress tolerance in Escherichia coli

Abstract

Small heat shock proteins (sHSPs) are heat shock proteins sized 12–43 kDa that can protect proteins from denaturation, particularly under high temperature; sHSPs thus increase the heat tolerance capability of an organisms enabling survival in adverse climates. sHSP20 is overexpressed in Oenococcus oeni in response to low temperatures. However, we found that overexpression of sHSP20 in Escherichia coli BL21 increased the microbial survival ratio at 50 °C by almost 2 h. Adding sHSP20 to the glutamate dehydrogenase solution significantly increased the stability of the enzyme at high temperature (especially at 60–70 °C), low pH values (especially below 6.0), and high concentration of metal ions of Ga2+, Zn2+, Mn2+, and Fe3+. Notably, the coexpression of sHSP20 significantly enhanced soluble expression of laccase from Phomopsis sp. XP-8 (CCTCCM209291) in E. coli without codon optimization, as well as the activity and heat stability of the expressed enzyme. In addition to the chaperone activity of sHSP20 in the gene containing host in vivo and the enzyme heat stability in vitro, our study indicated the capability of coexpression of sHSP20 to increase the efficiency of prokaryotic expression of fungal genes and the activity of expressed enzymes.

Graphical abstract



Carvedilol protection against endogenous Aβ-induced neurotoxicity in N2a cells

Abstract

Mutations in amyloid precursor protein (APP) and presenilin1 result in overproduction and accumulation of β-amyloid (Aβ) peptide, which has been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Carvedilol, a nonselective β-adrenergic receptor blocker used for treatment for heart failure and hypertension, has displayed its neuroprotective capacity due to its antioxidant property. In this study, we investigated whether Carvedilol has a neuronal protective effect against endogenous Aβ neurotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and Presenilin exon9 deletion mutant (N2a/Swe.D9). Elevated levels of reactive oxygen species (ROS), protein carbonyls, and 4-HNE were found in N2a/Swe.D9 cells, which were ameliorated by administration of Carvedilol in a dose-dependent manner. In addition, the levels of ATP and mitochondrial membrane potential were reduced in N2a/Swe.D9 cells, which were restored by treatment with Carvedilol. N2a/Swe.D9 cells displayed increased vulnerability to H2O2-induced cell death and apoptosis, which could be attenuated by Carvedilol. Mechanistically, we found that Carvedilol prevented apoptosis signals through reducing cytochrome C release and the level of cleaved caspase-3. Taken together, our findings suggest a possible use of Carvedilol in AD treatment.



Targeted heat activation of HSP promoters in the skin of mammalian animals and humans

Abstract

The use of highly inducible HSP promoters for exerting spatial and/or temporal control over the expression of therapeutic transgenes has long been discussed. Localized and time-limited induction of the heat shock response may potentially also be of medical interest. However, such applications would require targeted delivery of heat doses capable of activating HSP promoters in tissues or organs of interest. Accessible areas, including the skin and tissues immediately underneath it, may be most readily targeted. A few applications for heat-directed or heat-controlled therapy in the skin might involve expression of proteins to restore or protect normal skin function, protein antigens for vaccination/immunotherapy, vaccine viruses or even systemically active proteins, e.g., cytokines and chemokines. A review of the literature relating to localized heat activation of HSP promoters and HSP genes in the skin revealed that a multitude of different technologies has been explored in small animal models. In contrast, we uncovered few publications that examine HSP promoter activation in human skin. None of these publications has a therapeutic focus. We present herein two, clinically relevant, developments of heating technologies that effectively activate HSP promoters in targeted regions of human skin. The first development advances a system that is capable of reliably activating HSP promoters in human scalp, in particular in hair follicles. The second development outlines a simple, robust, and inexpensive methodology for locally activating HSP promoters in small, defined skin areas.



Antioxidant effect of myricitrin on hyperglycemia-induced oxidative stress in C2C12 cell

Abstract

Hyperglycemia induced oxidative stress inside the cells. Myricitrin, as an antioxidant plant-derived component, may be useful in hyperglycemia. Hence, the aim of this study was conducted to evaluate the antioxidant effects of myricitrin on hyperglycemia-induced oxidative damage in myotubes (C2C12 cells). In this experimental study, mouse myoblast cell line (C2C12) was obtained and divided into five groups: control, hyperglycemia, hyperglycemia + myricitrin 1, 3, and 10 μM. After treatment period for 48 h, cells were collected, homogenized, and centrifuged at 2000 rpm for 10 min. All samples were kept at − 80 °C until experimental and real-time PCR assessments were performed. Hyperglycemia increased malondialdehyde (MDA) (p < 0.05), total antioxidant capacity (TAC) (p < 0.001), and cellular apoptosis, and decreased levels of superoxide dismutase (SOD), catalase (CAT) (p < 0.01), myotube glycogen content (p < 0.05), glucose transporter type 4 (Glut-4), and cellular viability (p < 0.001). Myricitrin administration improved SOD (p < 0.05), CAT (p < 0.01), muscle cell's glycogen content (p < 0.01), Glut-4 gene expression (p < 0.001), Thiazolyl blue tetrazolium bromide (MTT) (p < 0.05), and Bax to Bcl-2 ratio (p < 0.001), and reduced MDA (p < 0.05) compared to hyperglycemia group. In conclusion, hyperglycemic condition induced oxidative stress along with cellular apoptosis, and myricitrin improved these disorders. Also, low and moderate doses of myricitrin are more efficient on skeletal muscle cells exposed to hyperglycemic statues than a high concentration of this antioxidant agent.



Exendin-4 improves ER stress-induced lipid accumulation and regulates lipin-1 signaling in HepG2 cells

Abstract

Lipin-1 performs dual function during lipid metabolism, i.e., it functions as a transcriptional coactivator and as a phosphatidate phosphatase during triglyceride biosynthesis. We investigated whether exendin-4 prevented endoplasmic reticulum (ER) stress-induced hepatic steatosis and whether the protective effects of exendin-4 were associated with lipin-1 signaling. Tunicamycin and thapsigargin, ER stress inducers, increased triglycerides (TG) content and expression of genes encoding lipid droplet surface proteins. Exendin-4 decreased the expression of ER stress markers phosphorylated PKR like ER kinase (PERK), phosphorylated inositol-requiring enzyme 1 alpha (IRE1α), and glucose-regulated protein 78 kDa (GRP78) proteins and spliced X-box binding protein 1 (XBP-1s) mRNA and increased the expression of genes encoding lipolytic enzymes hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and VLDL assembly-associated proteins microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB) in tunicamycin-pretreated cells. Moreover, exendin-4 significantly decreased lipin-1β/α ratio by increasing SFRP10 and increased lipin-1 nuclear localization. The decrease in lipin-1β/α ratio was also observed in SIRT1 and AMPK agonist-treated cells. These data suggest that exendin-4 improves ER stress-induced hepatic lipid accumulation by increasing lipolysis and VLDL assembly, which is partially mediated by the regulation of lipin-1 signaling.



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Vom Punkt zur Fläche in der Messung des Wasseräquivalents der Schneedecke – Mehrwert von Cosmic-Ray Neutron Sensoren in der regionalen Schneemodellierung

Zusammenfassung

In dieser Arbeit wird die Messmethode des Cosmic Ray Neutron Sensing (CRNS) zur Erfassung des Wasseräquivalents der Schneedecke (SWE) in Gebirgsräumen vorgestellt. Dieses kontaktlose und wartungsarme Verfahren ermöglicht die kontinuierliche und zerstörungsfreie Erfassung der Schneedecke in einem Bereich von mehreren Hektar. Im Rahmen einer Messkampagne in den Tiroler Alpen wurde die Methode weiterentwickelt. In der darauf aufbauenden schneehydrologischen Modellierung eines bepegelten Kopfeinzugsgebiets war die Zielsetzung, den Skalensprung zwischen Punktmessung und Modellauflösung zu überbrücken. Die räumliche und zeitliche Entwicklung der Schneedecke wurde über drei Wintersaisonen hindurch beobachtet. Es wurden (i) kontinuierliche konventionelle SWE-Messungen auf der Punktskala, (ii) insgesamt 17 Messkampagnen (Schneeschächte, terrestrisches Laserscanning) sowie (iii) kontinuierliche CRNS-Messungen durchgeführt. Der Vergleich mit Laserscan basierten SWE-Werten zeigt, dass CRNS auch in hochalpinem Terrain mit entsprechend hohen Schneemengen eine kontinuierliche und verlässliche Abschätzung des SWE erlaubt. Die Übertragbarkeit zwischen Wintersaisonen mit unterschiedlichen Schneeverteilungen ist sehr gut. Kein zeitlich konstanter Zusammenhang wurde dagegen zwischen Laserscan basierten SWE-Werten und der konventionellen kontinuierlichen Messung gefunden. Auch in einem anschließenden Kalibrierexperiment wird der Mehrwert der CRNS Messungen im Vergleich zur konventionellen Messung deutlich. Hierfür wurde ein Energiebilanz basiertes schneehydrologisches Modell in Bezug auf (i) Abflussmessungen, (ii) fernerkundungsbasierte Schneebedeckungskarten (basierend auf Landsat-8 und Sentinel-2A Aufnahmen) und (iii) in-situ Schneemessungen kalibriert. Dabei wurden jeweils konventionelle bzw. auf CRNS basierte SWE-Daten verwendet. Bei der Nutzung des CRNS basierten SWE Datensatzes zeigte sich klar dessen Vorteil. Die gute Übertragbarkeit zwischen Messung und Modell führt zu einer verbesserten Simulation der Schneedecke.



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Aktuell



Replicate after reading: on the extraction and evocation of cultural information

Abstract

Does cultural evolution happen by a process of copying or replication? And how exactly does cultural transmission compare with that paradigmatic case of replication, the copying of DNA in living cells? Theorists of cultural evolution are divided on these issues. The most important objection to the replication model has been leveled by Dan Sperber and his colleagues. Cultural transmission, they argue, is almost always reconstructive and transformative, while strict 'replication' can be seen as a rare limiting case at most. By means of some thought experiments and intuition pumps, I clear up some confusion about what qualifies as 'replication'. I propose a distinction between evocation and extraction of cultural information, applying these concepts at different levels of resolution. I defend a purely abstract and information-theoretical definition of replication, while rejecting more material conceptions. In the end, even after taking Sperber's valuable and important points on board, the notion of cultural replication remains a valid and useful one. This is fortunate, because we need it for certain explanatory projects (e.g., understanding cumulative cultural adaptations).



Synthetic versus analytic approaches to protein and DNA structure determination

Abstract

The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries.



Infection and inflammation imaging standardization: the EANM guidelines



SPECT vs. PET in cardiac innervation imaging: clash of the titans

Abstract

Purpose

We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on 18F-labeled tracers.

Results

Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue 123I-meta-Iodobenzylguanidine (123I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages including improved spatio-temporal resolution and intrinsic quantifiability. Compared to their 11C-labeled counterparts with a short half-life (20.4 min), novel 18F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging. The longer half-life of 18F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such 18F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal.

Conclusions

18F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or 11C-labeled tracers in the long run.



18 F-FDG or 68 Ga/ 18 F-PSMA PET/CT in recurrent renal cancer?



Leg Ulcers: Expanding the Differential

Abstract

Purpose of Review

Cutaneous lower extremity ulcerations are major source of morbidity and mortality. It can be challenging to identify an underlying etiology. This review provides a systematic framework for generating a thoughtful differential diagnosis and workup approach. We also highlight recent discoveries in the pathophysiology and treatment approaches of leg ulceration.

Recent Findings

Venous leg ulceration is being treated with a number of promising new modalities including pentoxifylline, statin therapy, topical timolol, connexin-43 peptide antagonists, photodynamic therapy, and punch grafting. The role of vitamin K deficiency is gaining prominence with regard to calciphylaxis.

Summary

Recognition of key risk factors and subtle physical exam findings can serve as clues to the underlying mechanism of cutaneous ulceration and direct a targeted workup for underlying systemic disease that may be ameliorated with appropriate therapy.



Urticaria, Urticarial Vasculitis, Angioedema, and Related Diseases

Abstract

Purpose of Review

Dermatologists are frequently called to evaluate patients with urticaria in the emergency room, urgent care clinics, and hospitals. Many acute urticarial eruptions will resolve without long-term sequelae; however, there are red flags that clinicians must be aware of.

Recent Findings

First-line treatment for acute urticaria is regular dose H1 antagonists; however, the dose can be increased up to fourfold for refractory disease. Short courses of corticosteroids should be avoided as rebound urticaria is common upon discontinuation. Urticarial vasculitis presents with persistent, atypical urticaria, burning, and residual lesions. The most common extra-cutaneous manifestation of urticarial vasculitis is musculoskeletal involvement. Schnitzler syndrome is a rare, severe condition but new evidence provides promise for use of biologic therapies.

Summary

Acute spontaneous urticarial eruptions are commonly encountered in hospitalized patients. This review provides readers with the tools needed to delineate benign eruptions from more concerning conditions.



Livedoid Vasculopathy: an Updated Review

Abstract

Purpose of Review

To highlight the most recent findings in the literature on livedoid vasculopathy while providing a basic review of the disease.

Recent Findings

Lipoprotein(a) and plasminogen activator inhibitor continue to develop evidence supporting their involvement in the pathogenesis of livedoid vasculopathy. Systematic review of the literature has revealed that anticoagulants are the most commonly reported treatments in case series followed by anabolic steroids, antiplatelets, and intravenous immunoglobulins. No randomized or controlled trials have been performed studying treatment efficacy.

Summary

The literature continues to support the hypothesis that livedoid vasculopathy is a disease of hypercoagulability and impaired fibrinolysis. There is no established treatment for livedoid vasculopathy, although a wide variety of treatments have been used to achieve partial or complete remission. Anticoagulants continue to be the most commonly reported treatment in the literature with rivaroxaban used most frequently.



Pain Management in Patients with Chronic Wounds

Abstract

Purpose of Review

Chronic wounds are increasing in prevalence and are often associated with significant pain, which can have a major impact on quality of life. Safe and effective pain management can be challenging, an unfortunate reality that is highlighted by the ongoing opioid crisis. This review aims to provide an evidence-based framework for pharmacologic and non-pharmacologic pain management in patients with chronic wounds.

Recent Findings

As reflected in the new CDC guidelines, no study has shown that long-term opioid use mitigates chronic pain. Non-pharmacologic therapies, including virtual reality and acupuncture, have shown efficacy and are promising adjuvant therapies for pain management.

Summary

Non-opioid pharmacotherapies and non-pharmacologic therapies are preferable to opioids for chronic pain related to non-healing wounds. The experience of pain is a subjective and complex biopsychosocial process that necessitates a rational, personalized, and often multimodal approach to management.



Virus-like particles (VLP) in prophylaxis and immunotherapy of allergic diseases

Abstract

Background

Apart from active allergen avoidance, immunotherapy is regarded as the most effective form of treatment available for type I allergies. Such treatments involve the administration of allergen preparations in various forms and by various routes. Virus-like particles (VLPs) offer a very effective platform for immunization with the allergen and are characterized by high immunogenicity, low allergenicity and high clinical efficacy. Formulations that include Toll-like receptor ligands, T cell stimulatory epitopes and/or depot-forming adjuvants appear to enhance activation of the relevant immune cells. Short nucleotide sequences including CpG motifs have also been intensively explored as potent stimulators of dendritic cells and B cells.

Methods

The present paper is based on a systematic literature search in PubMed and MEDLINE, and focuses on the pertinent immunological processes and on clinical data relating to use of VLPs and CpG motifs for the treatment of allergic rhinitis (AR).

Results

Many published studies have reported positive clinical results following administration of VLPs, either alone or in combination with CpG motifs and, in some cases, even in the absence of the allergen-specific allergen.

Conclusions

These results indicate that VLPs modulate immune responses in ways which underline their exceptional promise as a platform for the immunotherapy of allergic disorders. However, clinical evaluations remain limited, and further large-scale and longer-term studies will be necessary to substantiate the efficacy and safety of these novel therapies.



Molecular Classification and Management of Rare Pediatric Embryonal Brain Tumors

Abstract

Purpose of Review

Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents significant diagnostic challenges, particularly for tumor entities that are rarely encountered in clinical practice and for which diagnostic criteria were poorly defined. This review will provide an update on the evolving characterization and treatment of rare EBTs.

Recent Findings

Rapid advances in genomic tools have led to the discovery of robust molecular markers, and identification of novel tumor types and subtypes for almost all major categories of pediatric brain tumors. These developments have had significant impact on improving the diagnostic classification of the rare EBTs, particularly for tumors with newly recognized C19MC alterations, central nervous system primitive neuroectodermal tumors (CNS-PNET), and pineoblastoma (PB).

Summary

These important developments in the clinical and molecular understanding of rare EBTs are paving the way for novel therapeutic strategies and improved clinical management.



Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies

Abstract

Purpose of Review

For patients with locally advanced rectal cancer, neoadjuvant hypofractionated short-course radiation remains an underutilized regimen in the USA. We review the current clinical literature highlighting the relative merits of short-course radiation, along with modern neoadjuvant strategies that incorporate its use.

Recent Findings

As compared to long-course chemoradiation with delayed surgery, short-course radiation with early surgery offers similar oncologic efficacy for locally advanced rectal cancer patients. Delaying surgery after short-course radiation decreases post-operative complications as compared to early surgery and improves tumor downstaging. Delaying surgery also offers the opportunity to administer neoadjuvant systemic therapy, which may help increase local-regional tumor response and potentially decrease distant relapse rates, the latter a persisting problem in rectal cancer treatment.

Summary

Short-course radiation, either with immediate or with delayed surgery, represents an appealing treatment alternative to long-course chemoradiation for patients with locally advanced rectal cancer.



Updated Guidelines for the Treatment of Acquired Aplastic Anemia in Children

Abstract

Purpose of Review

This review aimed to provide updated guidelines for the management of children with acquired aplastic anemia (AA), particularly focusing on hematopoietic stem cell transplantation (HSCT).

Recent Findings

Failure-free survival for children with aplastic anemia has been shown to be better after bone marrow transplantation (BMT) from matched or one-locus mismatched related donors (MRD/1MMRD) than after immunosuppressive therapy (IST). A combination of the absence of minor paroxysmal nocturnal hemoglobinuria clones and short telomere length was identified as a strong predictor of a poor response to IST. Upfront HSCT from matched unrelated donors (MUD) and MRD was recently demonstrated to have comparable outcomes. Moreover, unrelated cord blood transplantation (UCBT) and haploidentical HSCT have shown promising outcomes, and the fludarabine/melphalan-based regimen has resulted in excellent survival without poor graft function.

Summary

BMT from MRD/1MMRD is the treatment of choice. When a MRD/1MMRD is not available, upfront BMT from a MUD should be considered for patients with only a slim chance of responding to IST. UCBT and haploidentical HSCT are promising options. This updated treatment algorithm should improve overall outcomes for children with AA.



Bladder Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

Abstract

Purpose of Review

Here, we will review and summarize the current status and emerging data supporting the use of trimodality therapy as an alternative to cystectomy for patients with muscle-invasive bladder cancer.

Recent Findings

There are no randomized-controlled data comparing radical cystectomy with bladder preserving trimodality therapy available for comparison. However, observational data suggests acceptable bladder preservation and functional outcomes in patients receiving bladder preserving trimodality therapy as well as similar oncologic outcomes in select patients compared to radical cystectomy. Future trials are focusing on new techniques and novel therapeutics in patients with bladder cancer.

Summary

Bladder preserving trimodality therapy results in satisfactory quality of life and comparable disease outcomes for select patients with muscle-invasive urothelial carcinoma of the bladder compared to cystectomy.



Tyrosine Kinase Inhibitor-Induced Hypertension

Abstract

Purpose of Review

The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios.

Recent Findings

Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension.

Summary

The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.



Wu, Fei 吳飛, “Disintegration” of Human Relations: Family-country’s Anxiety in the Tradition of Hylomorphism 人倫的 “解體” : 形質論傳統中的家國焦慮



Moral Artisanship in Mengzi 6A7

Abstract

This essay investigates the structure and meaning of the Mengzi's 孟子 analogical inferences in Mengzi 6A7. In this chapter, he argues that just as the perceptual masters allowed the discovery of our senses' uniform preferences, the sages enabled us to recognize our hearts' universal preferences for "order (li 理) and righteousness (yi 義)." Regarding an unresolved question of how the sages help us understand our hearts' preferred objects as such, I propose a spectator-based moral artisanship reading as an alternative to an evaluator-focused moral connoisseurship view: the sages are moral artisans who refine their moral achievements, and people's uniform approval of their achievements—firmly associated with "order and righteousness"—demonstrates our hearts' same natural preferences for them. Furthermore, I argue that this chapter's conclusion—we and the sages are of the same kind with natural moral preferences—implies the necessity of our transition from passive spectators to active moral performers for moral self-cultivation.



Shaping the New Woman: The Dilemma of Shen in China’s Republican Period

Abstract

As a response to China's experiences with European colonialism, a number of political and intellectual movements emerged during the late 19th and early 20th century, with the objective to inculcate certain desirable qualities into its citizens, particularly the modern woman. This article compares the modern Chinese concept of the physical body (shenti 身體) with that of the traditional ideal Confucian body (shen 身). By emphasizing shenti as a vessel for objective knowledge amid the construction of a politically-desired social order, Chinese activists adapted a Western, binary mind-body concept. However, this in turn gave rise to a number of social problems. Greed, moral corruption, and prostitution ultimately revealed the modern shenti concept to be a volatile construct. Through this process, the female body came to stand for the revolutionary promises of modernity, but also served as a focus for collective delusions, as well as a meeting point for all manners of anxieties.



Fraser, Chris, The Philosophy of the Mòzǐ: The First Consequentialists



The Development of the Chinese Doctrine of the Nonidentity and Inseparability of the Body and the Soul—The Shenmielun ( On the Extinction of the Soul ) and Its Origins

Abstract

Fan Zhen's 范縝 (450–515) Shenmielun 神滅論 (On the Extinction of the Soul) is a famous Chinese treatise discussing the body-soul problem. This discussion had been advocated by Huan Tan 桓譚 (43 BCE–28 CE) and Wang Chong 王充 (27–100). However, their views did not receive positive attention: at the beginning of the Eastern Han dynasty, their intellectual weight was far from significant enough to spur the court's interest in the topic. During the time of Fan Zhen, Emperor Wu of Liang (Liang Wudi 梁武帝, 464–549), a keen protector of the thought of dharma, raised the question of the soul and the body to a political level, making it the focus of academic debate. The aim of this article is to give a comprehensive account on the development of the idea of the nonidentity and inseparability of the body and the soul as promulgated by Fan Zhen and his predecessors from the perspective of the history of ideas.



Kim, Jung-Yeup: Z hang Zai’s Philosophy of Qi: A Practical Understanding



Empathy for Non-Kin, the Faraway, the Unfamiliar, and the Abstract––An Interdisciplinary Study on Mencian Moral Cultivation and a Response to Prinz

Abstract

This article challenges the pessimistic view that empathy and other fellow feelings are biased and erratic motivation for morality. By discussing Mencius' account on how to develop empathy from its biased and erratic beginnings, I argue that empathy can be extended to less common objects, such as non-kin, the faraway, the unfamiliar, and the abstract. The extension facilitated by empathy in turn enhances one's moral cognition toward the sufferings of less common objects; the extension also helps to include less common objects into one's circle of care. I respond to critics of empathy such as Prinz by highlighting the dynamic cultivational process of empathy that they overlook, and further point out that empathy can be cultivated so as to provide a remedy for the biases that no emotion is immune to. This article contributes to the ongoing discussion on moral cultivation in the Chinese philosophy community and the dispute over empathy's role in morality in contemporary ethics.



Ma, Lin, and Jaap van Brakel, Fundamentals of Comparative and Intercultural Philosophy



Lin, Weijie 林維杰, Z hu Xi and Classics Hermeneutics 朱熹與經典詮釋



W ang Fuzhi’s Criticism of Buddhism and Its Limitations

Abstract

Wang Fuzhi's 王夫之 remarks on Buddhism have not been given sufficient attention despite increasing research on him. The few works on this topic either focus on just one aspect of his view of Buddhism or fail to disclose the purpose and uniqueness of his attack of it. This essay analyzes his view of Buddhism comprehensively, in particular his insight into the paradox of Buddhist universal love and his rejection of Buddhist retribution and reincarnation from Confucian righteousness and qi 氣-monism. In addition, it also explores the reason, context, and limitations of his criticism, that is, his reaction to the popular approach of "understanding Confucian classics through learning Buddhism" in the late Ming 明, his response to Zongmi's 宗密 criticism of Confucian cosmology and human nature, and his misunderstanding of some Buddhist concepts. Yet his criticism is still illuminating to our understanding of the interaction of Confucianism with Buddhism and other religions.



Yang, Rur-bin 楊儒賓, Zhuangzi as Confucian 儒門內的莊子



Incongruent Names: A Theme in the History of Chinese Philosophy

Abstract

This essay is meant to shed light on a discourse that spans centuries and includes different voices. To be aware of such trans-textual resonances can add a level of historical understanding to the reading of philosophical texts. Specifically, we intend to demonstrate how the notion of the ineffable Dao 道, prominently expressed in the Daodejing 道德經, informs a long discourse on incongruent names (ming 名) in distinction to a mainstream paradigm that demands congruity between names and what they designate. Thereby, we trace the development of the idea of the ineffable Dao quite differently from modern mystical interpretations. We show how, in an early Chinese context, it first gives rise to a sociopolitical critique of the incongruity underlying socially constructed names in the Zhuangzi 莊子, then to a discourse on the incongruity between moral virtues and names in Xuanxue 玄學 philosophy, and eventually to Sengzhao's 僧肇 claim that a perceived congruence of names with things does not entail actual congruence between names and reality.



Goblet cell produced retinoic acid suppresses CD86 expression and IL-12 production in bone marrow derived cells

Abstract
Conjunctival goblet cell loss in ocular surface diseases is accompanied by increased number of IL-12 producing antigen presenting cells (APC) and increased IFN- expression. This study tested the hypothesis that mouse conjunctival goblet cells produce biologically active retinoic acid (RA) that suppresses CD86 expression and IL-12 production by myeloid cells. We found conditioned media from cultured conjunctival goblet cells (CjCM) suppressed stimulated CD86 expression, NF-κB p65 activation and IL-12 and IFN- production in unstimulated and LPS-stimulated cultured bone marrow derived cells containing a mixed population of APCs. Goblet cell conditioned OVA-loaded APCs suppressed IFN- production and increased IL-13 production in co-cultured OTII cells. The goblet cell suppressive activity is due in part to their ability to synthesize RA from retinol. Conjunctival goblet cells had greater expression of aldehyde dehydrogenases Aldh1a1 and a3 and ALDEFLUOR activity than cornea epithelium lacking goblet cells. The conditioning activity was lost in goblet cells treated with an ALDH inhibitor, and an RARα antagonist blocked the suppressive effects of CjCM on IL-12 production. Similar to RA, CjCM increased expression of suppressor of cytokine signaling 3 (SOCS3) in bone marrow derived cells. SOCS3 silencing reversed the IL-12 suppressive effects of CjCM. Our findings indicate that conjunctival goblet cells are capable of synthesizing RA from retinol secreted by the lacrimal gland into tears that can condition APCs. Evidence suggests goblet cell RA may function in maintaining conjunctival immune tolerance and loss of conjunctival goblet cells may contribute to increased Th1 priming in dry eye.

Delineating the origins, developmental programs and homeostatic functions of tissue-resident macrophages

Abstract
A literature covering 150 years of research indicates that macrophages are a diverse family of professional phagocytes that continuously explore their environment, recognize and scavenge pathogens, unfit cells, cell debris as well as metabolites, and produce a large range of bioactive molecules and growth factors. A new paradigm suggests that most tissue-resident macrophages originate from fetal precursors that colonize developing organs and self-maintain independently of bone-marrow derived cells throughout life. The differentiation of these precursors is driven by a core macrophage transcriptional program and immediately followed by their specification through expression of tissue-specific transcriptional regulators early during embryogenesis. Despite our increasing understanding of ontogeny and genetic programs that shape differentiation processes and functions of macrophages, the precise developmental trajectories of tissue-resident macrophages remain undefined. Here, I review current models of fetal hematopoietic waves, possible routes of macrophage development and their roles during homeostasis. Further, transgenic mouse models are discussed providing a toolset to study the developmentally and functionally distinct arms of the phagocyte system in vivo.

Surface Noise

Abstract
In this paper, I argue that the dominant view of musical sampling embodies an impoverished conception of the expressive capabilities of sampling. There are two respects in which it goes wrong. First, it overlooks the possibility of samples representing their sample sources. Second, it overlooks the possibility of samples that are not instances of their sample sources. En route to bringing out why the dominant view is impoverished, I introduce a theoretical framework that illuminates some of the ways in which sample-based musical works can function as realistic representations of their sample sources.

Conversations on Art and Aesthetics

Conversations on Art and Aesthetics MaesHans oup. 2017. pp. 336. £30 (hbk)

Editorial Board

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s):



Differential Diagnosis in Dermatology, 4th edition, Ashton, Leppard, Cooper. CRC Press, Taylor & Francis Group, Boca Raton, FL (2014), 466 pages. $49.95.

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Ryan Bunney



Cutaneous vasculitis in rheumatologic disease: Current concepts of skin and systemic manifestations

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Robert G. Micheletti

Abstract

Cutaneous vasculitis may be limited to the skin, a manifestation of systemic vasculitis, or a sign of an important underlying disease state. A thorough and systematic approach is required for accurate diagnosis and evaluation of such patients to enable appropriate management of the vasculitis and any associated condition. Occasionally, cutaneous vasculitis is a manifestation or presenting sign of connective tissue disease, such as systemic lupus erythematosus, Sjögren syndrome, or another condition. Such patients are at risk for poor outcomes related to systemic manifestations of vasculitis, as well as increased severity of the underlying disease. Recognition of this important subset of patients with skin vasculitis enables appropriate workup and successful management.



Psoriatic arthritis and the dermatologist: An approach to screening and clinical evaluation

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Arianna Zhang, Drew J.B. Kurtzman, Lourdes M. Perez-Chada, Joseph F. Merola

Abstract

Psoriatic arthritis is a common form of inflammatory arthritis that frequently accompanies psoriasis of the skin—up to 30% of patients with psoriasis are affected. Recognition of the clinical features of psoriatic arthritis is critical, as delayed detection and untreated disease may result in irreparable joint injury, impaired physical function, and a significantly reduced quality of life. Recent epidemiologic studies have also supported that psoriatic arthritis is associated with cardiometabolic and cerebrovascular comorbidities, including coronary heart disease, diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular accidents, further highlighting the importance of identifying affected patients. Dermatologists are poised for the early detection of psoriatic arthritis, as psoriasis predates its development in as many as 80% of patients. In an effort to further acquaint dermatologists and other clinicians with psoriatic arthritis, this review provides a detailed overview, emphasizing its salient clinical features, and discusses classification criteria, validated screening tools, and simple musculoskeletal examination maneuvers that may facilitate earlier detection and treatment of the disorder.



Inflammatory arthritis and crystal arthropathy: Current concepts of skin and systemic manifestations

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Mahdieh Fazel, Joseph F. Merola, Drew J.B. Kurtzman

Abstract

Systemic inflammatory disorders frequently involve the skin, and when cutaneous disease develops, such dermatologic manifestations may represent the initial sign of disease and may also provide valuable prognostic information about the underlying disorder. Familiarity with the various skin manifestations of systemic disease is therefore paramount and increases the likelihood of accurate diagnosis, which may facilitate the implementation of an appropriate treatment strategy. An improvement in quality of life and a reduction in the degree of morbidity may also be a realized benefit of accurate recognition of these skin signs. With this context in mind, this review highlights the salient clinical features and unique dermatologic manifestations of rheumatoid arthritis, adult-onset Still's disease, and the crystal arthropathy, gout.



Less common rheumatologic disorders: Current concepts of skin and systemic manifestations

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Taraneh Paravar

Abstract

The cutaneous manifestations of the common rheumatologic disorders, such as systemic lupus erythematosus, dermatomyositis, and systemic sclerosis, are well known. In contrast, the dermatologic findings of less common rheumatologic disorders, including Sjögren syndrome, mixed connective tissue disease, and relapsing polychondritis, are less widely known. The cutaneous manifestations of these connective tissue disorders are reviewed.



Clinical significance of autoantibodies in dermatomyositis and systemic sclerosis

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Danielle M. Tartar, Lorinda Chung, David F. Fiorentino

Abstract

Autoimmune connective tissue diseases, including dermatomyositis and systemic sclerosis, have a heterogeneous clinical presentation and prognosis; moreover, their clinical features are often incomplete and overlap with other rheumatic disorders, which can make diagnosis and prognostic stratification challenging. Specific autoantibodies have been associated with certain clinical findings as well as prognostic implications, and many new associations have been made over the last decade. Although patient populations manifest considerable heterogeneity, autoantibodies can be used to help predict clinical features, prognosis, and response to therapy. In this review, the clinical and prognostic implications associated with disease-specific autoantibodies in dermatomyositis and scleroderma are summarized with an emphasis on how the clinician can use this information for patient care.



Raynaud’s phenomenon: Current concepts

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Thomas Stringer, Alisa N. Femia

Abstract

Raynaud's phenomenon (RP) is a transient, acral, vasospastic phenomenon that manifests with characteristic color changes. This vasospasm, classically triggered by cold temperatures, may also be driven by shifts in temperature, climate, or emotional state. Primary RP (PRP) is a common condition without severe sequelae. Secondary RP (SRP), which may be driven by vascular, autoimmune, hematologic, or endocrine etiologies, can result in digital ulceration, irreversible ischemia and necrosis, and secondary infection. This review delineates the clinical manifestations of both primary and secondary RP, as well as the current understanding of RP epidemiology and pathogenesis. Proper examination, including nailfold capillary microscopy, and laboratory workup for secondary causes of RP are also discussed. The traditional armamentarium of therapies used for RP, as well as newer medical and surgical options, is also summarized with particular regard to the clinical evidence for their efficacy.



Eosinophilic fasciitis: Current concepts

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Nicole Fett, Megan Arthur

Abstract

Eosinophilic fasciitis (EF) is an uncommon connective tissue disease characterized by abrupt onset of edema, followed by progressive induration of primarily the distal extremities. Patients may exhibit inflammatory arthritis, joint contractures, decreased mobility, and nerve entrapment. Almost half of patients with EF may have coexisting morphea plaques. Classic laboratory studies display peripheral eosinophilia, hypergammaglobulinemia, and elevated inflammatory markers. EF is included in the spectrum of scleroderma like disorders and may be difficult to distinguish from other sclerosing skin disorders. Full-thickness biopsy containing muscle and fascia is considered the gold standard for diagnosis and reveals sclerosis of the middeep dermis, subcutaneous fat, and thickening of the fascia. Magnetic resonance imaging (MRI) has been increasingly utilized to augment diagnostic capabilities. Ultimately, the diagnosis of EF relies upon the combination of characteristic clinical, laboratory, imaging, and histologic findings. Although some patients experience spontaneous remission, systemic corticosteroids (SCS) are the mainstay of treatment. Patients who fail to improve with SCS alone require the addition of a second immunosuppressive drug. Additionally, although data are limited, there is evidence to suggest that initial combination therapy with SCS and methotrexate (MTX) may be most beneficial.



Morphea: Current concepts

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Stephanie Florez-Pollack, Elaine Kunzler, Heidi T. Jacobe

Abstract

Morphea is an inflammatory, sclerosing skin disorder that can involve the underlying soft tissues. Although the cause of morphea remains poorly investigated, genetic predisposition, immune dysregulation, and environmental factors have been implicated. Morphea is associated with cosmetic and functional sequelae, and internal organ involvement is rare. Early diagnosis and treatment are imperative to minimize damage such as limitation of range of motion. This review summarizes advances in diagnosis and treatment of morphea, allowing clinicians to better serve patients with this condition.



Systemic sclerosis: Current concepts of skin and systemic manifestations

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): David R. Pearson, Victoria P. Werth, Lisa Pappas-Taffer

Abstract

Systemic sclerosis is an uncommon autoimmune connective tissue disease with multiorgan system involvement and significant associated morbidity and mortality. Cutaneous signs and clinical manifestations are of particular importance, as they may be recognized before systemic manifestations, allowing earlier risk stratification into the limited and diffuse cutaneous subtypes, as well as earlier initiation of treatment. Important cutaneous manifestations include Raynaud's phenomenon, digital ulcers, cutaneous sclerosis, calcinosis cutis, telangiectasias, pruritus, and dyspigmentation. Despite investigation of a wide variety of treatments, no FDA-approved pharmacologic therapies exist for systemic sclerosis, and data from high-quality studies are limited. In the following review, we will discuss skin-directed therapies. Although there is evidence to support specific treatments for Raynaud's phenomenon, digital ulcers, and cutaneous sclerosis, there are limited rigorous studies evaluating the treatment of other cutaneous signs and clinical manifestations. Additional randomized-controlled trials and large observational studies are necessary to develop future evidence-based treatment options.



Dermatomyositis: Current concepts

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Ivan Bogdanov, Jana Kazandjieva, Razvigor Darlenski, Nikolai Tsankov

Abstract

Dermatomyositis (DM) is a multifactorial chronic autoimmune disorder with characteristic skin changes and involvement of different organ systems, including the muscles, blood vessels, joints, esophagus, and lungs. In terms of epidemiology, DM affects both children and adults. It is most often observed beyond the age of 40, but there is also a peak of incidence between 5 and 12 years of age. The current paradigm describing the pathophysiology of DM is an autoimmune attack on affected organs that is triggered by environmental factors such as UV exposure, drugs, infection, and lifestyle decisions in genetically susceptible individuals. Importantly, DM is also regarded as a paraneoplastic phenomenon, as cancer may precede, occur concurrently with, or follow the development of the clinical signs of DM. The cutaneous manifestations of DM can be categorized as pathognomonic, characteristic, compatible, less common, rare, recent, and nonspecific. The treatment of DM is a difficult task due to its rarity, its multiple phenotypes, and the fact that the disease may affect multiple organs and is commonly treatment-refractory. The lack of randomized, controlled intervention trials and, until recently, the insufficiency of validated, clinically meaningful outcome instruments in part contribute to the lack of approved treatments.



Cutaneous lupus erythematosus: Reflecting on practice-changing observations over the past 50 years

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Jeffrey P. Callen

Abstract

Several historical observations have led to the current understanding of the diagnosis, evaluation, and management of patients with cutaneous lupus erythematosus. Seminal advances in the management of this disease include the development of a classification system for cutaneous lupus, the use of a validated scoring system to assess patient disease activity, and expansion of knowledge of the action spectrum of this disease; further, observations regarding certain medications as potential causes of subacute cutaneous lupus erythematosus, the risk of progression from "pure" cutaneous disease to systemic disease, and traditional versus newer therapies are reviewed with closer inspection.



Rheumatologic dermatology

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Drew Kurtzman



Table of Contents

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s):



Frederic E. Mohs, MD, and the history of zinc chloride

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Charles DePaolo

Abstract

The history of zinc chloride therapy before and including Frederic E. Mohs' (1910-2002) early contributions to dermatologic oncology is presented. In 1932, Mohs devised a method of cutaneous surgery that employed zinc-chloride paste to devitalize basal or squamous cell carcinoma. Because zinc chloride coagulates malignant tissue without destroying cellular architecture, he described the surgery and its preservative effect as the fixed-tissue method. This method involved the serial removal of devitalized malignant tissue and the freezing and histologic examination of each layer; the process was continued until a cancer-free plane was reached. In 1953, a modified version of the micrographic system, the fresh-tissue method, was introduced. For improved efficiency, Mohs retained the systematic mapping of a neoplasm but eliminated the chemical escharotic. Although the fresh-tissue method has become the preferred treatment mode, zinc-chloride paste therapy remains in use today. Although the history of Mohs micrographic surgery is well documented, its background has not received sufficient attention. This paper surveys the chemical synthesis of zinc chloride, the formulation of zinc-chloride paste as a cutaneous escharotic, and the extent to which Mohs' method compares with those of 19th and early 20th century predecessors.



Surgery at the BEST Medical Center—Clyde’s Adventures in BEST Land: Down the Rabbit Hole

Publication date: July–August 2018

Source: Clinics in Dermatology, Volume 36, Issue 4

Author(s): Philip R. Cohen

Abstract

Dr. Ida Lystic is an assistant professor in the Division of Gastroenterology at the Byron Edwards & Samuel Thompson (BEST) Medical Center. Before becoming one of the BEST doctors, she completed her fellowship training at the Owen T. Henry and Eugene Rutherford (OTHER) Medical Center and her MD degree at the prestigious Harvey Medical School (which was recently renamed the Harvey Provider School). She is still challenged by the new electronic medical record system—LEGEND (also referred to as the Lengthy and Excessively Graded Evaluation and Nomenclature for Diagnosis), after the BEST discarded the SIMPLE system. Recently she became the deputy head of the Gastroenterology Fellowship Selection Committee and had to organize the candidate activities that included testing of new physicians' most important skill: the typing trial. Dr. Lystic's stepfather, Clyde S. Dale, MD, developed severe spinal stenosis and required surgery at the BEST Medical Center. The BEST, being a model of efficiency, has no schedulers to "interfere" with the patients' ability to schedule themselves for all their tests and book their surgery. Indeed, it took only 22 phone calls on Clyde's part to ensure that everything was properly calendared. Clyde's postoperative course was complicated by hypoxia and atrial fibrillation (which revealed that the BEST Rapid Response Team has no physician or midlevel practitioner), as well as a missed cerebrospinal fluid leak and an ulnar neuropathy secondary to inadequate elbow padding during surgery. Fortunately, however, Clyde's insurance coverage is excellent, and all of his bills have been paid.



Father Adam Wisniewski, MD and his work for lepromatous patients in India

Publication date: Available online 10 June 2018

Source: Clinics in Dermatology

Author(s): Andrzej Grzybowski, Kajetan Charzewski

Abstract

Father Adam Wiśniewski (1913–1987), who was a Pallotine and a medical doctor with specialization in Tropical Diseases, devoted his life to helping and curing leprosy patients in India. His life proved difficult and varied. He began his medical studies during World War II in occupied Warsaw. What is more, he participated in the Warsaw Uprising in 1944, for which he later received the Cross of Valour, one of the highest Polish commendations. He learned about leprosy in France and then moved to India to use his medical knowledge to treat lepers and stop the spread of the disease. He created a center for the impoverished at Jeevodaya, India which is still serves as a refuge for patients with leprosy.



Developing an Eczema Action Plan

Publication date: Available online 8 June 2018

Source: Clinics in Dermatology

Author(s): Moise L. Levy

Abstract

As physicians, we spend time learning about diseases and their management. The primary key to successful outcomes is the involvement of patients and their families in the care of conditions they seek our assistance for. For atopic dermatitis, all patients require frequent emollients for xerotic skin and care of the inflammation, which comes and goes frequently. The levels of care require vary by time and patient. Younger patients require the help of parents or other family members. A keen understanding of the timing and appropriate use of the various treatment modalities is required and is often confusing. Action plans, as used in the care of asthma, for instance, can be effectively integrated into the overall care instructions for atopic dermatitis and have been indispensible for many of my patients and their families. They are one concrete method for patient/family engagement in the overall care planning. The action plans can certainly be translated into languages appropriate for any practice environment. The following brief summary should be of use to those professionals considering use of this technique.



How I Learned to Stop Worrying and Love Machine Learning

Publication date: Available online 8 June 2018

Source: Clinics in Dermatology

Author(s): Sarah Mattessich, Michael Tassavor, Susan M. Swetter, Jane M. Grant-Kels

Abstract

Artificial intelligence and its machine learning capabilities are very promising technologies for dermatology and other visually-oriented fields due to their power in pattern recognition. Understandably, many physicians distrust replacing clinical finesse with unsupervised computer programs. Here we describe convolutional neural networks and discuss how this method of machine learning will impact the field of dermatology.



Assessment of chromium hyper-accumulative behaviour using biochemical analytical techniques of greenhouse cultivated Sonchus asper on tannery waste dump site soils

Abstract

Keeping the sources of pollution such as chromium (Cr) under a safe limit is a daunting challenge due to the negative impact of heavy metal bioaccumulation in vegetation and the concomitant human health exposure. We took a closer look at Sonchus asper by cultivating in the green house. It resulted in 80% germination when cultivated over nine different soils collected from the tannery dump site. The biochemical analytical techniques such as mass spectrometry indicated significant bioaccumulation of Cr in the plant tissue. As per the ICP-MS analysis, this annual herb resulted in the accumulation of 601 mg kg−1 of total Cr with 212 mg kg−1 in its shoot from soil samples containing up to 41 mg kg−1 of hexavalent Cr. The energy dispersive X-ray (EDX) spectroscopy of S. asper revealed a higher level of S element indicating a sulfate-Cr binding relation. Elevated content of Cr in soil (73,721 ± 65 mg kg−1) caused biochemical changes in the shoot of S. asper as indicated by the disappearance of Fourier transform infrared spectroscopy (FTIR) bands at 935 and 872 cm−1 and further revealing aliphatic –CH2 appearing as anti-symmetry νa(CH2) and symmetric vibration νs(CH2) at the band of 2920 and 2850 cm−1, respectively.



Hydrogel applications for adsorption of contaminants in water and wastewater treatment

Abstract

During the last decade, hydrogels have been used as potential adsorbents for removal of contaminants from aqueous solution. To improve the adsorption efficiency, there are numerous different particles that can be chosen to encapsulate into hydrogels and each particle has their respective advantages. Depending on the type of pollutants and approaching method, the particles will be used to prepare hydrogels. The hydrogels commonly applied in water/wastewater treatment was mainly classified into three classes according to their shape included hydrogel beads, hydrogel films, and hydrogel nanocomposites. In review of many recently research papers, we take a closer look at hydrogels and their applications for removal of contaminants, such as heavy metal ion, dyes, and radionuclides from water/wastewater in order to elucidate the reactions between contaminants and particles and potential for recycling and regeneration of the post-treatment hydrogels.

Graphical abstract



Seed priming with Se mitigates As-induced phytotoxicity in rice seedlings by enhancing essential micronutrient uptake and translocation and reducing As translocation

Abstract

We laid down this investigation to explore the promotive and antagonistic aspect of selenium (Se) when supplemented through seed priming technology in rice before sowing into arsenic (As) free and As spiked soil. Findings suggest that As stress inhibits germination (35.38%), seedling growth (38.19%), chlorophyll content by 42.31%, and reduced translocation of iron, zinc, manganese by 19.40, 17.33, and 18.40% respectively, in the seedlings of unprimed seeds. Seedlings of unprimed seeds also had greater As translocation into the aerial part beside repressing micronutrient translocation, significantly. On the contrary, Se-primed seeds had higher germination (27.82%), longer root length (20.14%), greater chlorophyll content beside having greater translocation of iron, zinc, manganese in shoots along with restricting As translocation in rice seedlings by confining more As in the root, in a significant manner (p < 0.05 level) than the unprimed seedlings grown in identical stress. On the other hand, seedlings of Se-primed seeds grown alike the control also had higher germination % (7.08%), root and shoot length with significantly less proline, and hydrogen peroxide content in root and shoot. Findings indicate that seed priming with Se executes dual role, a growth promoting and antagonism in a more practical and farmer-friendly way to mitigate As-induced toxicity and enhance growth in rice seedlings.



Biologics for pityriasis rubra pilaris treatment: A review of the literature

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Monica Napolitano, Damiano Abeni, Biagio Didona

Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous skin disease that is often refractory to conventional therapies. The off-label use of biologics, such as anti–tumor necrosis factor, anti–interleukin (IL) 12/IL-23, and anti–IL-17 agents, has been proven successful in the past 2 decades for PRP treatment. Our aim was to analyse the literature for the use of biologics in PRP treatment. We conducted a review by performing PubMed and ClinicalTrials.gov searches. Sixty-eight articles met our selection criteria and are herein discussed. Out of 86 PRP patients, the vast majority were treated with anti–tumor necrosis factor, anti–IL-12/IL-23, or anti–IL-17 biologics, either alone or in combination therapy. A marked-to-complete response was observed in 50%-78%, a partial response in 11%-25%, and no or poor response in 11%-25%. This review has several limitations, including small sample sizes and the lack of shared study design criteria. In some instances, PRP might have resolved spontaneously. Further, the presence of concomitant therapy or the lack of detailed data on previous treatments, makes it difficult to strictly define a therapeutic role per se of specific biologics in PRP. This review shows that biologics may be regarded as a tool for PRP treatment alone or in combination therapy although clinical trials are needed to better assess their efficacy and safety.



Dermatology Calendar

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s):



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Arash Mostaghimi, Cara Joyce



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Luna Aksoy



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Michael Benzaquen, Luca Borradori, Simone Cazzaniga, Philippe Berbis, Laurence Feldmeyer



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Shamir Geller, Noa Kremer, Tal Zeeli, Eli Sprecher



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Eric L. Simpson, Nick J. Reynolds, Carsten Flohr, Amy S. Paller, Jonathan I. Silverberg, Michel J. Cork, Emma Guttman-Yassky, Alan D. Irvine



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

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Adam Daunton, Jonathan M.R. Goulding



A simple method to facilitate fat removal from full-thickness skin grafts

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Marina Zoéga Hayashida, Mauro Yoshiaki Enokihara, Sérgio Henrique Hirata, Ival Peres Rosa



Dermoscopy for the detection and safe extraction of an intracutaneous foreign body

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Sidharth Sonthalia, Abhijeet Kumar Jha, Feroze Kaliyadan



Dermoscopy is a useful bedside tool for the evaluation of cutaneous loxoscelism

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Cristián Navarrete-Dechent, Sergio Álvarez-Véliz



Correction

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s):



Modernizing regulation of cosmetic products: Reintroduction of the Personal Care Products Safety Act

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Harrison P. Nguyen, Wilma F. Bergfeld, Howard P. Forman, Donald V. Belsito, Jean L. Bolognia



How data can deliver for dermatology

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Katrina Abuabara, Maryam M. Asgari, Suephy C. Chen, Robert P. Dellavalle, Sunil Kalia, Aaron M. Secrest, Jonathan I. Silverberg, James A. Solomon, Martin A. Weinstock, Jashin J. Wu, Mary-Margaret Chren, Epidemiology Expert Research Group



Dermatology, climate change, and the perils of attacks on expertise

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Saami Khalifian, Misha Rosenbach



The “dermatologist recommended” label: Is it meaningful?

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Mary E. Lohman, Peter A. Lio, Shuai Xu



Shortage of lidocaine with epinephrine: Causes and solutions

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Brandon Bodie, Robert T. Brodell, Stephen E. Helms



Real-world evidence–What is it and does it matter for approval of drugs?

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): William H. Eaglstein



Is there a doctor onboard?: The ethical conundrum of a specialist asked to provide in-flight medical assistance

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Sunil H. Adwani, Preeti Jhorar, Jane M. Grant-Kels



Consultative teledermatology in the emergency department and inpatient wards: A survey of potential referring providers

Publication date: August 2018

Source: Journal of the American Academy of Dermatology, Volume 79, Issue 2

Author(s): Justin Cheeley, Suephy Chen, Robert Swerlick



Testing environmental Kuznets curve hypothesis in G7 countries: the role of renewable energy consumption and trade

Abstract

This study has been conducted to examine the impact of trade, economic growth, and renewable energy on environmental degradation in G7 countries. The data consist of the years 1991–2016. We employed the panel unit root test and co-integration test, along with cross-sectional dependence and cross-sectionally augmented IPS unit root test by Pesaran (J Appl Econ 22:265–312, 2007). We also employed dynamic ordinary least squares, fully modified ordinary least squares, and fixed effect ordinary least squares regression. The result concluded that all the variables are co-integrated in the long run and all the variables create a significant effect on CO2 emission. This study implies that economic growth and trade increases the CO2 emission in the long run whereas the renewable energy consumption reduces the CO2 emission in the long run. The result also provides support for the Environmental Kuznets curve hypothesis in G7 countries.



Organic carbon content and humus composition after application aluminum sulfate and rice straw to soda saline-alkaline soil

Abstract

The soil organic carbon accumulation in soda saline-alkaline soil and the humus composition changes with application of aluminum sulfate and rice straw were investigated by the controlled simulative experiments in laboratory. For evaluating the amelioration effect, organic carbon content and humus composition in soda saline-alkaline soil were investigated with different application amounts of rice straw and aluminum sulfate. Potassium dichromate oxidation titration (exogenous heat) method and Kumada method were used to analyze the contents of organic carbon and humus composition, respectively. The transformation of soil organic matter in the saline-alkali soil during the amelioration has been clarified in this paper. The results demonstrated that the contents of soil organic carbon were significantly increased (13–92%) with different application amounts of rice straw and aluminum sulfate. The contents of free fraction and combined fraction of humus and their compositions (humic acid and fulvic acid) were increased with different application amounts of rice straw. The free fraction of humus was increased more dramatically. Due to aluminum sulfate application, free fraction of humus and humic acid (HA) was transformed to combined fraction partially. Free HA was changed to be P type with rice straw application. With aluminum sulfate application, free form of HA was changed from type P to type Rp. For rice straw application, combined HA only was transferred within the area of type A. Aluminum sulfate addition had no significant effect on the type of combined form of HA. With the same amount of rice straw application, the contents of soil organic carbon were increased by increasing the amount of aluminum sulfate application. Both rice straw and aluminum sulfate applications could reduce the humification degree of free and combined fraction of HA. According to the types of HA, it could be concluded that humus became younger and renewed due to the application of rice straw and aluminum sulfate.



Application of Escherichia coli antibiotic resistance patterns for contamination source identification in watershed

Abstract

Spatial correlation of pollution of the water resource in Taipei, Taiwan, were examined by analyzing the antibiotic resistance patterns (ARPs) of 96 Escherichia coli colonies, which were isolated from 7 sampling sites in 3 river sections. The ARPs were the growth patterns of isolated E. coli colonies in the medium with seven kinds of antibiotics, including ampicillin, chlortetracycline, erythromycin, oxytetracycline, streptomycin, tetracycline, and salinomycin of different concentrations. The results showed that the survival rate of E. coli decreased with increasing concentration of antibiotics; however, various ARPs under different antibiotics of different concentrations significantly increased both the useful information and complexities. Hierarchical cluster analysis (HCA) and two-stage principal component analysis (PCA) were applied to analyze the spatial correlations and interrelations of distinct ARPs among sampling sites in this study. It was found that the seven sampling sites can be categorized into three groups which may represent three possible pollution characteristics.



Effects on Eichhornia crassipes under Zn stress

Abstract

Eichhornia crassipes is a macrophyte widely used in phytoremediation, demonstrating a high ability to remove metals from water. The aim of this work was to evaluate its enzymatic detoxification strategies and metal accumulation when it is exposed to different Zn concentrations (0, 2, 4, 6, and 9 ppm) for periods of 24, 48, and 72 h. Zn concentration in roots was significantly higher than in aerial parts. Independently of the treatment, in the first 48 h, concentrations of photosynthetic pigments were not affected. However, a significant increase (between 19 and 34%) in Chl-b concentrations for all treatments was observed at 72 h. Carotenoid concentration was not affected during the first 48 h, while at 72 h, there was a significant increase regarding the control (between 11 and 24%) for all treatments. Malondialdehyde concentration in aerial parts and roots was not affected during the experiment. Nonetheless, a significant increase in the enzymatic activity of the antioxidant system was observed. Results suggest that Zn could have potential antioxidant properties, which may result in the activation of different antioxidant enzymes involved in the protection against metal stress.



Development of a modeling pipeline for the prediction of hemodynamic outcome after virtual mitral valve repair using image-based CFD

Abstract

Purpose

Severe mitral valve regurgitation can either be treated by a replacement or a repair of the valve. The latter is recommended due to lower perioperative mortality and better long-term survival. On the other hand, recurrence rates after mitral valve repair are high compared to those after replacements and the repair intervention can cause induced mitral valve stenosis. So far, there are no methods to predict the hemodynamic outcome of a chosen treatment or to compare different treatment options in advance. To overcome this, diastolic mitral valve hemodynamics are simulated using computational fluid dynamics after different virtual treatments of the valve.

Methods

The left ventricular geometry of one patient was reconstructed using trans-esophageal echocardiography and computed tomography data. Pre-op hemodynamics are simulated using a referenced wall model to avoid expansive modeling of wall motion. Subsequently, the flow structures are compared to in vivo measurements. After manipulating the patient-specific geometry in order to mimic a restrictive mitral annuloplasty as well as a MitraClip intervention, hemodynamics results are calculated.

Results

Good agreements exist between calculated pre-op hemodynamics and in vivo measurements. The virtual annuloplasty did not result in any remarkable change of hemodynamics. Neither the pressure drop nor the velocity field showed strong differences. In contrast, the virtual MitraClip intervention led to a complete change in blood flow structures as well as an elevated pressure drop across the valve.

Conclusion

The presented approach allows fast simulation of the diastolic hemodynamic situation before and after treatment of a mitral valve insufficiency. However, this approach is limited to the early diastolic phase of the cardiac cycle and needs to be validated using a larger sample size.



A novel animal model for residence time evaluation of injectable hyaluronic acid-based fillers using high-frequency ultrasound-based approach



Assessment of seafood contamination under the marine strategy framework directive: contributions of the German environmental specimen bank

Abstract

Descriptor 9 (D9) of the European Union Marine Strategy Framework Directive refers to the compliance of contaminant levels in fish and other seafood of a defined marine region or subregion with human health threshold values. This requires georeferenced samples that are often difficult to obtain when relying on commercial fisheries or programs designed for monitoring human exposure. The present study examines whether georeferenced samples of blue mussel (Mytilus edulis) and eelpout (Zoarces viviparus) fillet of the German environmental specimen bank (ESB) can be used in this context. The suitability of the ESB samples, procedures, and analytical methods is evaluated with respect to D9 requirements. Based on ESB data for the D9 relevant contaminants Pb, Cd, Hg, ∑4 PAHs, PCDD/Fs, dioxin-like (dl)-PCBs, and indicator non-dl-PCBs and the potentially relevant substances TBT, PFOS, PBDE, and HBCDD, the Good Environmental Status for D9 is assessed at the ESB sites in the North and Baltic Seas. The overall evaluation indicates that ESB samples are suitable for D9 assessment with the limitation that only coastal areas of the North and Baltic Seas are covered. Over a period of up to 30 years, concentrations of the D9 relevant contaminants were well below the maximum levels allowed for human consumption.



Stellenwert der Phototherapie in der Behandlung des chronischen Pruritus

Zusammenfassung

Die Phototherapie und Photochemotherapie (PUVA) sind wichtige Säulen in der Behandlung von entzündlichen Hauterkrankungen wie Psoriasis und atopischer Dermatitis sowie des kutanen T‑Zell-Lymphoms (z. B Mycosis fungoides/Sezary-Syndrom). Viele dieser Hauterkrankungen gehen mit quälendem Pruritus einher. Auch bei systemischen Erkrankungen der Niere und Leber sowie des endokrinen und blutbildenden Systems kann Pruritus ein belastendes Symptom der betroffenen Patienten sein. Die Behandlung mit ultraviolettem Licht kann nicht nur spezifische Hautveränderungen bessern, sondern auch den Pruritus vieler Hautkrankheiten sowie vieler systemischer Erkrankungen reduzieren. Die meist sehr gute antipruritische Wirkung, die bekannten und bei richtiger Durchführung geringen Nebenwirkungen sowie die Möglichkeit des Einsatzes bei Erwachsenen jeden Alters, Schwangeren/Stillenden und unter bestimmten Bedingungen auch bei Kindern machen die Phototherapie zu einer wertvollen Behandlungsmöglichkeit bei chronischem Pruritus unterschiedlicher Ursache. Der Einsatz der Phototherapie sollte daher früh erwogen werden, wenn lokaltherapeutische Maßnahmen nicht ausreichen, um den Pruritus zu lindern.



Digitalisierung in der Medizin

Zusammenfassung

Nach einer zweijährigen Übergangsfrist stellt die Datenschutz-Grundverordnung (DS-GVO) der Europäischen Union mit Wirkung zum 25. Mai 2018 ein europaweit gültiges und dem nationalen Recht gegenüber vorrangiges Datenschutzrecht dar. In diesem Zuge finden in Deutschland zudem ergänzend die Regelungen des Bundesdatenschutzgesetzes (BDSG) in der ab dem 25. Mai 2018 gültigen Fassung Anwendung. Dies hat auch Konsequenzen für Arztpraxen, die sich den neuen Herausforderungen des Datenschutzrechtes stellen müssen.



Effect of Prior Biologic Use on Cost-Effectiveness of Brodalumab vs. Ustekinumab for Treatment of Moderate-to-Severe Psoriasis in the United States

Abstract

Introduction

Clinical trials have shown brodalumab to have better efficacy than ustekinumab for the treatment of moderate-to-severe psoriasis. An estimation of the cost-effectiveness of brodalumab vs. ustekinumab is warranted and may be useful for treatment decision-making processes, especially in the context of the cost considerations of the current US healthcare system. Therefore, we compared the cost-effectiveness of brodalumab with ustekinumab for treatment of moderate-to-severe psoriasis in biologic-naïve and biologic-experienced patients in the USA.

Methods

An Excel-based economic model was developed to estimate and compare total annual costs to health plans associated with treatment with brodalumab vs. ustekinumab per achievement of Psorasis Area and Severity Index (PASI) 75, 90, and 100 for patients with moderate-to-severe psoriasis.

Results

For treatment with brodalumab vs. ustekinumab, total annual treatment costs per PASI 75, 90, and 100 were $31,106, $57,776, and $163,069, respectively, lower for a patient naïve to prior biologic treatment; they were $40,535, $65,472, and $223,610, respectively, lower for a patient experienced with prior biologic treatment. In an additional analysis among patients with and without prior biologic failure, they were $52,822, $93,309, and $365,606, respectively, lower for a patient with failure and they were $31,660, $57,128, and $164,996, respectively, lower for a patient without failure.

Conclusion

Compared to ustekinumab, treatment with brodalumab was associated with better cost-effectiveness ratios for biologic-naïve and experienced-patients and also patients with and without prior biologic treatment failure. The greater cost-effectiveness of brodalumab was most prominent for biologic-experienced and prior biologic treatment failure patients.

Funding

Ortho Dermatologics.



Prognostic value of 68 Ga PSMA I&T PET/CT SUV parameters on survival outcome in advanced prostat cancer

Abstract

Objective

To determine the association of 68 Ga-PSMA-I&T PET/CT SUV parameters with survival outcome in advanced prostate cancer patients.

Methods

A total of 148 consecutive patients mean age: 69.3 ± 7.8 years with advanced prostate cancer who underwent 68 Ga-PSMA-I&T PET/CT were included in this retrospective study. Data on previous treatments, serum PSA levels (ng/mL), 68 Ga-PSMA-I&T PET/CT findings metastases as well as survival data were recorded.

Results

Multivariate regression analysis revealed that Level 1 LN SUV/Liver SUV ratios > 2.17 (OR 4.262; 95% CI 1.104–16.453, p = 0.035), bone SUV > 10.7(OR 23.650; 95% CI 4.056–137.888, p < 0.001), bone SUV/spleen SUV ratio > 1.842 (OR 25.324; 95% CI 4.204–152.552, p < 0.001), highest SUVmax/liver SUV ratio > 2.32 (OR 19.309; 95% CI 1.730–209.552, p = 0.016) and highest SUVmax/spleen SUV ratio > 1.842 (OR 22.354; 95% CI 2.637–189.493, p = 0.004) were significant in the determination of increased mortality risk in advanced prostate cancer patients.

Conclusion

Our findings, for the first time in literature, provided evidence on potential utility of tracer uptake (SUV) cut-off values on 68 Ga-PSMA PET/CT in identification of the survival outcome of patients with metastatic disease and thereby in assisting in the selection of individualized therapeutic strategies tailored to the expected prognosis.