A case of an elderly man who required repeated repair of a ventricular septal defect and tricuspid rupture after blunt chest trauma

Abstract

Several cases of traumatic ventricular septal defect (VSD) have been reported. However, traumatic VSD complicated by tricuspid rupture is rare. We report a case of traumatic VSD with tricuspid rupture who required repeated repair of both conditions. A 69-year-old man was transferred to our hospital for emergent surgical repair of traumatic VSD and tricuspid rupture. Although emergent repair was performed, a new left-to-right shunt and moderate tricuspid regurgitation appeared during his postoperative course. A reoperation was performed 4 months after the first operation. The borders of the defect were very fibrotic and strong compared with those in the first operation. Surgical treatment of traumatic VSD should be postponed in hemodynamically stable patients. When emergent repair is performed, careful follow-up is necessary to diagnose new VSD.

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Live imaging analysis of human gastric epithelial spheroids reveals spontaneous rupture, rotation and fusion events

Abstract

Three-dimensional cultures of primary epithelial cells including organoids, enteroids and epithelial spheroids have become increasingly popular for studies of gastrointestinal development, mucosal immunology and epithelial infection. However, little is known about the behavior of these complex cultures in their three-dimensional culture matrix. Therefore, we performed extended time-lapse imaging analysis (up to 4 days) of human gastric epithelial spheroids generated from adult tissue samples in order to visualize the dynamics of the spheroids in detail. Human gastric epithelial spheroids cultured in our laboratory grew to an average diameter of 443.9 ± 34.6 μm after 12 days, with the largest spheroids reaching diameters of >1000 μm. Live imaging analysis revealed that spheroid growth was associated with cyclic rupture of the epithelial shell at a frequency of 0.32 ± 0.1/day, which led to the release of luminal contents. Spheroid rupture usually resulted in an initial collapse, followed by spontaneous re-formation of the spheres. Moreover, spheroids frequently rotated around their axes within the Matrigel matrix, possibly propelled by basolateral pseudopodia-like formations of the epithelial cells. Interestingly, adjacent spheroids occasionally underwent luminal fusion, as visualized by injection of individual spheroids with FITC–Dextran (4 kDa). In summary, our analysis revealed unexpected dynamics in human gastric spheroids that challenge our current view of cultured epithelia as static entities and that may need to be considered when performing spheroid infection experiments.

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Platelet–neutrophil interactions as drivers of inflammatory and thrombotic disease

Abstract

Neutrophils are well known for their role in infection and inflammatory disease and are first responders at sites of infection or injury. Platelets have an established role in hemostasis and thrombosis and are first responders at sites of vascular damage. However, neutrophils are increasingly recognized for their role in thrombosis, while the immunemodulatory properties of platelets are being increasingly studied. Platelets and neutrophils interact during infection, inflammation and thrombosis and modulate each other's functions. This review will discuss the consequences of platelet–neutrophil interactions in infection, thrombosis, atherosclerosis and tissue injury and repair.

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Deblurring sequential ocular images from multi-spectral imaging (MSI) via mutual information

Abstract

Multi-spectral imaging (MSI) produces a sequence of spectral images to capture the inner structure of different species, which was recently introduced into ocular disease diagnosis. However, the quality of MSI images can be significantly degraded by motion blur caused by the inevitable saccades and exposure time required for maintaining a sufficiently high signal-to-noise ratio. This degradation may confuse an ophthalmologist, reduce the examination quality, or defeat various image analysis algorithms. We propose an early work specially on deblurring sequential MSI images, which is distinguished from many of the current image deblurring techniques by resolving the blur kernel simultaneously for all the images in an MSI sequence. It is accomplished by incorporating several a priori constraints including the sharpness of the latent clear image, the spatial and temporal smoothness of the blur kernel and the similarity between temporally-neighboring images in MSI sequence. Specifically, we model the similarity between MSI images with mutual information considering the different wavelengths used for capturing different images in MSI sequence. The optimization of the proposed approach is based on a multi-scale framework and stepwise optimization strategy. Experimental results from 22 MSI sequences validate that our approach outperforms several state-of-the-art techniques in natural image deblurring.

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Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique

This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larg...

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Purpureocorticium microsporum (Basidiomycota) gen. et sp. nov. from East Asia

Abstract

A corticioid fungal species found in mountainous Taiwan, and Yunnan Province of China, is described as a new genus and new species: Purpureocorticium microsporum (Agaricomycetes, Basidiomycota). Morphological study and phylogenetic analyses based on sequence data respectively derived from the large subunit nuclear ribosomal RNA gene (LSU nrDNA) alone and the combined dataset of LSU nrDNA and translation elongation factor 1-α gene (tef1-α) indicated that Purpureocorticium does not belong to any clade of the Agaricomycetes. Purpureocorticium and P. microsporum are characterized by having a resupinate basidiocarp with smooth hymenial surface which turns purple in KOH, and becomes purplish after storage, microscopically having compact texture of subiculum, nodose-septate thin-walled generative hyphae, absence of cystidia, basidia subclavate with a median constriction, or utriform, bearing ovate-ellipsoid small-sized basidiospores, which are smooth and thin-walled, inamyloid, and nondextrinoid. The new combination Rhizochaete rubescens is proposed, based on morphological and phylogenetic evidences.

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Evaluation of the performance of three tenodesis techniques for the treatment of scapholunate instability: flexion-extension and radial-ulnar deviation

Abstract

Chronic scapholunate ligament (SL) injuries are difficult to treat and can lead to wrist dysfunction. Whilst several tendon reconstruction techniques have been employed in the management of SL instability, SL gap reappearance after surgery has been reported. Using a finite element model and cadaveric study data, we investigated the performance of the Corella, scapholunate axis (SLAM) and modified Brunelli tenodesis (MBT) techniques. Scapholunate dorsal and volar gap and angle were obtained following virtual surgery undertaken using each of the three reconstruction methods with the wrist positioned in flexion, extension, ulnar deviation and radial deviation, in addition to the ulnar-deviated clenched fist and neutral positions. From the study, it was found that, following simulated scapholunate interosseous ligament rupture, the Corella technique was better able to restore the SL gap and angle close to the intact ligament for all wrist positions investigated, followed by SLAM and MBT. The results suggest that for the tendon reconstruction techniques, the use of multiple junction points between scaphoid and lunate may be of benefit.

Graphical abstract

The use of multiple junction points between scaphoid and lunate may be of benefit for tendon reconstruction techniques.

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The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial

Abstract

Background

Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.

Methods

A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14.

Results

Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were −2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were −1.4 and −1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS.

Conclusion

Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP.

Trial registration

NCT02403479. Registered on March 1, 2015.

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Prospect of Using Cell Product for the Therapy of Skin Defects in Diabetes Mellitus

The effectiveness of autologous cell product in the therapy of skin burn wounds was studied in C57B1/6 male mice against the background of streptozotocin-induced diabetes mellitus. In animals with and without modeled diabetes mellitus, significant decrease in skin defect area was observed after single administration of the cell product (bone marrow multipotent mesenchymal stromal cells, fibroblasts or media conditioned by these cells).

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Heat Stress and Agonists of Muscarinic Cholinergic Receptors Modulate Sensitivity of Nicotinic Cholinergic Receptors in Soil Nematode Caenorhabditis elegans

We studied the effect of moderate heat stress (30oC) and muscarinic cholinergic receptor agonists arecoline and pilocarpine on sensitivity of the behavior of the nematode Caenorhabditis elegans of N2 line to the action of the agonist of nicotinic cholinergic receptor agonist levamisole. Heat stress and muscarinic cholinergic receptor agonists increased the sensitivity of swimming induced by mechanical stimulation to levamisole (32-64 μM), which manifested in dyscoordination of locomotor muscles during swimming and complete loss of ability to swim. Combined exposure to heat stress and muscarinic cholinergic receptor agonists revealed their synergism in the influence on sensitivity of swimming behavior to levamisole: heating to 30oC potentiated the effect of arecoline and arecoline potentiated the effect of heat stress. It is assumed, that the effect of heat stress on the sensitivity of nicotinic receptors is mediated by its effect on muscarinic receptors.

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Behavior Disorders Caused by Perinatal Hypoxia in Juvenile Rats and Their Correction with GABA Derivative

We studied the effects of acute normobaric hypoxia on postnatal day 2 (model of preterm pregnancy) on reflex activity and behavior of juvenile male Wistar rats and the possibility of correction of behavioral deficit by administration of GABA derivative Salifen after hypoxia. It is shown, that perinatal hypoxia impaired righting reflex and forelimb grip strength and increased motor activity in juvenile male rats. Administration of Salifen for 14 days in a dose of 15 mg/kg improved reflex activity and behavior of rats, which indicates the prospect of further study of the therapeutic efficacy of this drug on models of neonatal encephalopathy.

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The effectiveness of topical colloidal silver in recalcitrant chronic rhinosinusitis: a randomized crossover control trial

Abstract

Background

Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.

Methods

A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14.

Results

Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were −2.8 and 1.0 for saline and CS, respectively (p = 0.373). Similarly, mean 6-week change in LK scores were −1.4 and −1.1 for saline and CS, respectively (p = 0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS.

Conclusion

Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP.

Trial registration

NCT02403479. Registered on March 1, 2015.

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Multivariable prediction model for suspected giant cell arteritis: development and validation

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Intraocular pressure 1 year after vitrectomy in eyes without a history of glaucoma or ocular hypertension

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Spectropathology-corroborated multimodal quantitative imaging biomarkers for neuroretinal degeneration in diabetic retinopathy

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Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation

Publication date: Available online 24 November 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Kavit Amin, Alexandra L. Ball, Chandanpreet Chhina, Rebecca J. Edge, John P. Stone, William R. Critchley, Jason K. Wong, James E. Fildes
BackgroundPassenger leukocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.MethodsBilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice. Each limb from the same pig underwent a post-preservation intravascular flush with isotonic solution at either 2 or 6hrs. Venous effluent underwent flow cytometry to phenotype leukocyte populations, with additional quantification of cytokines and cell-free DNA.ResultsWe identified large populations of viable leukocytes in the flush effluent (8.65x10⁸ ±3.10x10⁸ cells at 2hrs and 1.02x10⁹ ±2.63x10⁸ at 6hrs). This comprised T cells, B cells, NK cells and monocytes. Post-preservation flush yielded significant concentrations of pro-inflammatory cytokines including IL-6, IL-18, GM-CSF, IL-1β, IL1α and CXCL-8 and mitochondrial DNA. The regulatory cytokine, IL-10 was undetectable.ConclusionsThis study supports the finding that a post-preservation flush removes leukocytes and inflammatory components that are responsible for direct presentation. This study also gives an indication of how ischaemia impacts on the inflammatory burden transferred to the recipient upon reperfusion.



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Intracellular trafficking of transforming growth factor β receptors

Abstract

Transforming growth factor β (TGFβ) family members signal via heterotetrameric complexes of type I (TβRI) and type II (TβRII) dual specificity kinase receptors. The availability of the receptors on the cell surface is controlled by several mechanisms. Newly synthesized TβRI and TβRII are delivered from the Golgi apparatus to the cell surface via separate routes. On the cell surface, TGFβ receptors are distributed between different microdomains of the plasma membrane and can be internalized via clathrin- and caveolae-mediated endocytic mechanisms. Although receptor endocytosis is not essential for TGFβ signaling, localization of the activated receptor complexes on the early endosomes promotes TGFβ-induced Smad activation. Caveolae-mediated endocytosis, which is widely regarded as a mechanism that facilitates the degradation of TGFβ receptors, has been shown to be required for TGFβ signaling via non-Smad pathways. The importance of proper control of TGFβ receptor intracellular trafficking is emphasized by clinical data, as mislocalization of receptors has been described in connection with several human diseases. Thus, control of intracellular trafficking of the TGFβ receptors together with the regulation of their expression, posttranslational modifications and down-regulation, ensure proper regulation of TGFβ signaling.

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The efficacy of recombinant turkey herpesvirus vaccines targeting the H5 of highly pathogenic avian influenza virus from the 2014–2015 North American outbreak

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Charles L. Balzli, Kateri Bertran, Dong-Hun Lee, Lindsay Killmaster, Nikki Pritchard, Perry Linz, Teshome Mebatsion, David E. Swayne
The outbreak of highly pathogenic avian influenza virus in North American poultry during 2014 and 2015 demonstrated the devastating effects of the disease and highlighted the need for effective emergency vaccine prevention and control strategies targeted at currently circulating strains. This study evaluated the efficacy of experimental recombinant turkey herpesvirus vector vaccines with three different inserts targeting the hemagglutinin gene of an isolate from the recent North American influenza outbreak. White leghorn chickens were vaccinated at one day of age and challenged with A/Turkey/Minnesota/12582/2015 H5N2 at 4 weeks of age. Birds were analyzed for survival, viral shedding at two and four days after infection, and specific antibody prior to challenge and from surviving birds. The three experimental vaccines demonstrated 100%, 45% and 15% survival with the most effective vaccine significantly reducing oral and cloacal viral shedding compared to all other groups and generated specific antibody prior to challenge with highly pathogenic avian influenza virus. More studies are needed using diverse H5Nx highly pathogenic virus isolates to fully determine the breadth of coverage against possible exposure strains, as well as possible impact of maternally derived antibody on protection and vaccine efficacy.



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Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Bikash Sahay, Natacha Colliou, Mojgan Zadeh, Yong Ge, Minghao Gong, Jennifer L. Owen, Melissa Valletti, Christian Jobin, Mansour Mohamadzadeh
Clostridium botulinum readily persists in the soil and secretes life-threatening botulinum neurotoxins (BoNTs) that are categorized into serotypes A to H, of which, serotype A (BoNT/A) is the most commonly occurring in nature. An efficacious vaccine with high longevity against BoNT intoxication is urgent. Herein, we developed a dual-route vaccine administered over four consecutive weeks by mucosal and parenteral routes, consisting of the heavy chain (Hc) of BoNT/A targeting dendritic cell peptide (DCpep) expressed by Lactobacillus acidophilus as a secretory immunogenic protein. The administered dual-route vaccine elicited robust and long-lasting memory B cell responses comprising germinal center (GC) B cells and follicular T cells (Tfh) that fully protected mice from lethal oral BoNT/A fatal intoxication. Additionally, passively transferring neutralizing antibodies against BoNT/A into naïve mice induced robust protection against BoNT/A lethal intoxication. Together, a targeted vaccine employing local and systemic administrative routes may represent a novel formulation eliciting protective B cell responses with remarkable longevity against threatening biologic agents such as BoNTs.



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Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Ine Wouters, Liesbet Van Heirstraeten, Stefanie Desmet, Stéphanie Blaizot, Jan Verhaegen, Herman Goossens, Pierre Van Damme, Surbhi Malhotra-Kumar, Heidi Theeten
BackgroundIn Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007–2011) to PCV13 (2011–2015) and to PCV10 (2015–2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance.Materials/methodsTwo infant populations aged 6–30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed.ResultsCulture-based (DCC: 462/760; 60.8% – AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% – AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 10⁶ copies/µl (95%CI = 3.9–9.2 × 10⁶, median = 3.5 × 10⁵); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively.ConclusionFour years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.

Graphical abstract

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Will we have new pertussis vaccines?

Publication date: Available online 24 November 2017
Source:Vaccine
Author(s): Camille Locht
Despite wide vaccination coverage with efficacious vaccines, pertussis is still not under control in any country. Two types of vaccines are available for the primary vaccination series, diphtheria/tetanus/whole-cell pertussis and diphtheria/tetanus/acellular pertussis vaccines, in addition to reduced antigen content vaccines recommended for booster vaccination. Using these vaccines, several strategies are being explored to counter the current pertussis problems, including repeated vaccination, cocoon vaccination and maternal immunization. With the exception of the latter, none have proven their effectiveness, and even maternal vaccination is not expected to ultimately control pertussis. Therefore, new pertussis vaccines are needed, and several candidates are in early pre-clinical development. They include whole-cell vaccines with low endotoxin content, outer membrane vesicles, new formulations, acellular vaccines with new adjuvants or additional antigens and live attenuated vaccines. The most advanced is the live attenuated nasal vaccine BPZE1. It provides strong protection in mice and non-human primates, is safe, even in immune compromised animals, and genetically stable after in vitro and in vivo passages. It also has interesting immunoregulatory properties without being immunosuppressive. It has successfully completed a first-in-man clinical trial, where it was found to be safe, able to transiently colonize the human respiratory tract and to induce immune responses in the colonized subjects. It is now undergoing further clinical development. As it is designed to reduce carriage and transmission of Bordetella pertussis, it may hopefully contribute to the ultimate control of pertussis.



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Experimental assessment of the Advanced Collapsed-cone Engine for scalp brachytherapy treatments

Publication date: Available online 24 November 2017
Source:Brachytherapy
Author(s): Brie Cawston-Grant, Hali Morrison, Ron S. Sloboda, Geetha Menon
PurposeTo experimentally assess the performance of the Advanced Collapsed-cone Engine (ACE) for ¹⁹²Ir high-dose-rate brachytherapy treatment planning of nonmelanoma skin cancers of the scalp.Methods and MaterialsA layered slab phantom was designed to model the head (skin, skull, and brain) and surface treatment mold using tissue equivalent materials. Six variations of the phantom were created by varying skin thickness, skull thickness, and size of air gap between the mold and skin. Treatment planning was initially performed using the Task Group 43 (TG-43) formalism with CT images of each phantom variation. Doses were recalculated using standard and high accuracy modes of ACE. The plans were delivered to Gafchromic EBT3 film placed between different layers of the phantom.ResultsDoses calculated by TG-43 and ACE and those measured by film agreed with each other at most locations within the phantoms. For a given phantom variation, average TG-43– and ACE-calculated doses were similar, with a maximum difference of (3 ± 12)% (k = 2). Compared to the film measurements, TG-43 and ACE overestimated the film-measured dose by (13 ± 12)% (k = 2) for one phantom variation below the skull layer.ConclusionsTG-43– and ACE-calculated and film-measured doses were found to agree above the skull layer of the phantom, which is where the tumor would be located in a clinical case. ACE appears to underestimate the attenuation through bone relative to that measured by film; however, the dose to bone is below tolerance levels for this treatment.



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Dosimetric impact of inter-observer catheter reconstruction variability in ultrasound-based high-dose-rate prostate brachytherapy

Publication date: Available online 24 November 2017
Source:Brachytherapy
Author(s): Alexandru Nicolae, Jure Murgic, Ivan Kruljac, Lior Dubnitzky, Laura D'Alimonte, Lin Lu, Aaron Cumal, Niki Law, Gerard Morton, Andrew Loblaw, Hans T. Chung, Ananth Ravi
PurposeTo investigate the dosimetric impact of interobserver catheter reconstruction variability in transrectal ultrasound–guided prostate high-dose-rate (HDR) brachytherapy.Methods and MaterialsTwenty consecutive patients with intermediate- or high-risk prostate cancer were treated with a single, 15-Gy HDR brachytherapy boost as part of this study. The treated plan was used as the study reference plan (PR). Three expert treatment planners (observers) manually reconstructed the catheter paths on the static three-dimensional transrectal ultrasound images, and new plans were generated from the updated positions (POBS); subsequently, the dwell time and positions from the POBS plans were superimposed on the PR catheter paths to evaluate the dosimetric effect of the interobserver variations (PEVAL). Plans from each group were stratified by observer and by number of catheters (12 or 16) and then compared using a one-way Kruskal–Wallis H test with post hoc Mann–Whitney U tests reserved for significant variations (α = 0.05).ResultsGreater than 98.9% of catheter reconstruction variations were <3 mm. When stratified by observer, there was a significant decrease (p << 0.05) in planning target volume (PTV) V100% and increases in the urethral Dmax between the POBS plans propagated to the PR catheter paths and dosimetry evaluated and PR plans only. Stratification of plans by catheter number showed nonclinically significant decreases in PTV V100%, and D90% and increases in urethral Dmax for the 12-catheter plans.ConclusionsLimiting interobserver variability, and its effects on prostate HDR brachytherapy plan quality, is critical to achieving good dosimetric outcomes; small variations in catheter reconstruction may translate to inadequate PTV coverage, excessive urethral dose, or both.



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Wound healing of cutaneous substance losses based on infectious, inflammatory and traumatic skin disorders: The experience of a center

Publication date: Available online 24 November 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): K. Khoshim, B. Hersant, C. Hotz, M. SidAhmed-Mezi, J.P. Meningaud
IntroductionThere is no reference available concerning the standard healing time based on dermatological diseases responsible for cutaneous substance losses. The aim of our study was to assess the healing time after surgical debridement of necrotizing fasciitis (NF), hidradenitis suppurativa (HS) and skin necrosis due to trauma (SNT) based on multiples existing co-morbidities among these patients to provide surgeons with accurate scientific data in order to inform and educate patients and nurses who are practicing care under the supervision of the surgeon.Materials and methodsThis was a retrospective study. The primary endpoint was the time for complete wound healing, which was calculated from the time of the last surgical procedure to the complete wound healing corresponding to the time of complete reepithelialization, when daily dressings were no longer needed.ResultA total of 107 patients were included. The mean time for complete wound healing was 64.94±31.55 days in patients with NF, 45.70±21.40 days in patients with SNT and 75.02±26.41 days in patients with HS (SNT versus NF, P=0.004** and SNT versus HS, P<0.0001**).ConclusionThe mean time for complete wound healing was 64.94 days in patients with NF, 45.70 days in patients with SNT, 75.02 days in patients with HS. This study can be considered as a referential based on the experience of a reference centre for these 3 pathologies (NF, HS, and SNT) whose aim is to inform plastic surgeons in order to anticipate the management or educate the patient.



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Characteristics of Trophoblasts in Long-Term Culture

We analyzed more than 40 cytotrophoblast cultures derived from cell islets that grew from trypsinized tissue fragments of placental microvilli. Phenotypic variability of trophoblasts was demonstrated. Changes in trophoblast morphology from epithelium-like or oval cells to bipolar and spindle-shaped or twisted and then to mesenchymal-like cells as well as intensive expression of cytokeratin-7 and vimentin attested to epithelial-mesenchymal transition of trophoblasts during in vitro culturing. Analysis of the expression of specific markers in long-term trophoblast culture (≥7 passages) revealed the possibility of culture contamination with other non-trophoblast cells including fibroblasts. High risk of trophoblast culture contamination with rapidly growing cells necessitates regular control of the cultures used in fundamental studies. Our experiments confirmed the possibility of long-term culturing of cells maintaining trophoblast properties. The identity and purity of 4 trophoblast cultures free from contamination and retaining the properties of pure culture during long-term (>10 passages) culturing in vitro were confirmed.

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Comparison of Different Methods of Purification and Concentration in Production of Influenza Vaccine

The overwhelming majority of influenza vaccines are prepared with the use of chicken embryo allantoic fluid. The presence of ovalbumin (this protein constitutes >60% total protein in the allantoic fluid) in the vaccine can lead to severe allergy. Hence, effective reduction of ovalbumin content is of crucial importance for vaccine production. We compared two methods of purification and concentration of influenza virus: zonal gradient ultracentrifugation and combined ultrafiltration/diafiltration and exclusion chromatography protocol, used for fabrication of seasonal vaccines. Combined chromatography is comparable with zonal centrifugation protocol by the results of ovalbumin removal (to meet standard requirements).

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Morphofunctional Properties of Human Platelets Treated with Silver Nanoparticles

We studied structural and functional properties of human platelets in the presence of nanosilver particles. Incubation with 0.05-5 μM silver nanoparticles suppressed platelet adhesion in a dose-dependent manner without affecting internal platelet structure; during adhesion, some granules were not exocytized. Spontaneous platelet activation was observed at nanoparticle concentrations 15-100 μM. Addition of 1-5 μM nanosilver to cells undergoing adhesion blocked massive platelet degranulation, but did not prevent the formation of lamellopodia. The maximum number of preserved granules in platelets was revealed in the presence of 2.5-5 μM silver nanoparticles: 50% after platelet preincubation with silver nanoparticles and 75-77% after stabilization of adherent platelets with silver nanoparticles.

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Formation of Tissue-Engineered Construct of Human Cartilage Tissue in a Flow-Through Bioreactor

We performed culturing of a cell-engineered construct of human cartilage tissue consisting of biopolymer microstructured collagen-containing hydrogel, human adipose tissue mesenchymal stromal cells, and induction chondrogenic culture medium in a specially designed flow-through bioreactor. On day 16 of the experiment, human adipose tissue mesenchymal stromal cells acquired flattened shape typical for chondroblasts, demonstrated high proliferative activity, and formed extracellular matrix. The observed histological changes in the cultured system attested to the beginning of the formation of a tissue-engineered construct of human cartilage tissue.

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Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) with Additional Protein Domain Synthesized in E. coli : In Vivo Osteoinductivity in Experimental Models on Small and Large Laboratory Animals

Recombinant human bone morphogenetic protein-2 with an additional s-tag domain (s-tag-BMP-2) synthesized in E. coli is characterized by higher solubility and activity than the protein without additional s-tag domain, which increases the yield during purification and simplifies protein introduction into the osteoplastic materials. The high osteoinductivity of the demineralized bone matrix with s-tag-BMP-2 was shown on the model of regeneration of cranial defects of a critical size in mice and on the model of implantation of porous titanium matrix into defects of femoral and tibial bones in rabbits.

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Neuroprotective Effect of σ1-Receptors on the Cell Model of Huntington’s Disease

Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.

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Experimental Study of Statistical Stability of Cardiointerval Samples

In 1947 M. A. Bernstein proposed a hypothesis about "repetition without repetition" in biomechanics that was confirmed in psychophysiology by the Eskov—Zinchenko effect. This effect can be applied to all parameters (except the parameters of the neuromuscular system) of human body homeostasis. For instance, this instability can be demonstrated for repeated samples of cardiointerval parameters (and other homeostasis parameters) of the human cardiorespiratory system. Within the framework of the new theory of chaos and self-organization, a method is proposed for calculation of matrices of paired comparisons of cardiointerval samples for assessing the physiological status of the human body and changes in homeostasis. Statistical instability of cardiointerval samples and their statistical distribution functions f(x) for successive cardiointerval samples in one subject is proven.

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Focal Unilateral Traumatic brain injury Causes Delayed Neurodegenerative Changes in the Brain of Rats

A cascade of pathological changes in the intact hemisphere developed in rats 6 months after focal unilateral traumatic brain injury: neuronal degeneration, hyperexpression of α-synuclein, APP (β-amyloid peptide precursor) protein, and glutamine synthetase in cells other than astrocytes. The development of these changes in the contralateral hemisphere indicated the emergence of extensive delayed neurodegenerative processes in the brain after traumatic brain injury, which were characteristic of diseases associated with pathological aging.

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Complex Analysis of Diffusion Transport and Microstructure of an Intervertebral Disk

We studied the relationship between diffusion transport and morphological and microstructural organization of extracellular matrix of human intervertebral disk. Specimens of the lumbar intervertebral disks without abnormalities were studied ex vivo by diffusion-weighed magnetic resonance imaging, histological and immunohistochemical methods, and electron microscopy. Distribution of the diffusion coefficient in various compartments of the intervertebral disk was studied. Significant correlations between diffusion coefficient and cell density in the nucleus pulposus, posterior aspects of annulus fibrosus, and endplate at the level of the posterior annulus fibrosus were detected for each disk. In disks with nucleus pulposus diffusion coefficient below 15×10^-4 mm²/sec, collagens X and XI were detected apart from aggrecan and collagens I and II. The results supplement the concept on the relationship between the microstructure and cell composition of various compartments of the intervertebral disk and parameters of nutrient transport.

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Effect of Native and Modified Apolipoprotein A-I on DNA Synthesis in Cultures of Different Cells

Culturing of bone marrow cells in serum-free RPMI-1640 medium for 24 h was accompanied by a decrease in the rate of [3H]-thymidine incorporation into DNA. Addition of native apolipoprotein A-I (apoA-I) or plasma LDL and HDL to the culture medium increased this parameter. In contrast to native apoA-I, its modified form decelerated DNA synthesis in bone marrow cells. A similar inhibitory effect of modified protein was observed in cultures of human embryonic kidney cells (HEK293) and in rapidly proliferating mouse macrophage cell line ANA-1. The only exclusion was human myeloid cell line U937: neither native nor modified apoA-I affected DNA synthesis in these cells. Thus, the regulatory effects of apoA-I are tissue-specific; this protein can produce either stimulatory or inhibitory effect on DNA biosynthesis in cells depending on its conformation.

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Diagnostic accuracy of coronary opacification derived from coronary computed tomography angiography to detect ischemia: first validation versus single-photon emission computed tomography

Abstract

Background

Estimation of functional relevance of a coronary stenosis by fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) has recently provided encouraging results. Due to its limited availability, the corrected contrast opacification (CCO) decrease and the transluminal attenuation gradient (TAG) were suggested as less complex alternatives. The aim of the present study was to assess the accuracy of CCO decrease and TAG to predict ischemia as assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

Results

This retrospective study included 72 patients who underwent hybrid CCTA/SPECT MPI with at least one coronary artery stenosis. Of 127 vessels with a coronary stenosis in CCTA, 38 (30%) were causing ischemia in its subtending myocardium. The area under the curve (AUC) for CCO decrease to predict ischemia was 0.707 with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 74, 64, 85, 47, and 67%, respectively. For TAG, the AUC was 0.469.

Conclusions

CCTA-derived CCO decrease but not TAG predicts ischemia in SPECT MPI. The negative predictive value of CCO decrease of 85% may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.

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Evaluation of the novel TSPO radiotracer [ 18 F] VUIIS1008 in a preclinical model of cerebral ischemia in rats

Abstract

Background

In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [¹⁸F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO.

Methods

Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[¹⁸F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([¹⁸F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([¹⁸F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats.

Results

MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [¹⁸F] VUIIS1008 and [¹⁸F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [¹⁸F] DPA714 uptake showed a mild uptake increase compared to [¹⁸F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [¹⁸F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats.

Conclusions

Altogether, these results suggest that [¹⁸F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.

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Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma

Abstract

Background

Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.

Case presentation

Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.

Conclusions

We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.

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HIV serostatus knowledge and serostatus disclosure with the most recent anal intercourse partner in a European MSM sample recruited in 13 cities: results from the Sialon-II study

Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to identify factors associated with HIV serostatus disclosure to...

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Infectious Complications following Breast Reconstruction Using Tissue Expanders in Patients with Atopic Dermatitis

Summary: Infectious complications represent one of the most prominent factors contributing to tissue expander (TE) loss in breast reconstruction procedures. Several patient characteristics that increase the risk for surgical-site infection or TE infection have been reported, but no study has focused on the relationship between atopic dermatitis (AD) and TE infection or surgical-site infection. Recently, we investigated 203 cases of breast reconstruction surgeries performed using TEs and noted that all 3 patients who had AD developed infectious complications that ultimately led to TE removal. Considering its pathophysiology, it is likely that patients with AD relatively easily develop infectious complications due to barrier dysfunction, abnormalities in innate immune responses, or colony formation by Staphylococcus aureus. Particular caution should be exercised for breast reconstruction using man-made materials in cases complicated by AD.

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Author Index

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Subject Index

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Instructions for Contributors

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TOC

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Calendar

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Editorial Board

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Calendar Listings

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Do Residency Selection Factors Predict Radiology Resident Performance?

Publication date: Available online 24 November 2017
Source:Academic Radiology
Author(s): Vikas Agarwal, Gregory M. Bump, Matthew T. Heller, Ling-Wan Chen, Barton F. Branstetter, Nikhil B. Amesur, Marion A. Hughes
Rationale and ObjectivesThe purpose of our study is to determine what information in medical student residency applications predicts radiology residency success as defined by objective clinical performance data.Materials and MethodsWe performed a retrospective cohort study of residents who entered our institution's residency program through the National Resident Matching Program as postgraduate year 2 residents and completed the program over the past 2 years. Medical school grades, selection to Alpha Omega Alpha (AOA) Honor Society, United States Medical Licensing Examination (USMLE) scores, publication in peer-reviewed journals, and whether the applicant was from a peer institution were the variables examined. Clinical performance was determined by calculating each resident's cumulative major discordance rate for on-call cases the resident read and gave a preliminary interpretation. A major discordance was defined as a difference between the preliminary resident and the final attending interpretations that could immediately impact the care of the patient. A multivariate logistic regression was performed to determine significant variables.ResultsTwenty-seven residents provided preliminary reports on call for 67,145 studies. The mean major discordance rate was 1.08% (range 0.34%–2.54%). Higher USMLE Step 1 scores, publication before residency, and election to AOA Honor Society were all statistically significant predictors of lower major discordance rates (P values 0.01, 0.01,  and <0.001, respectively).ConclusionsOverall resident performance was excellent. There are predictors that help select the better performing residents, namely higher USMLE Step 1 scores, one to two publications during medical school, and election to AOA in the junior year of medical school.



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Diagnostic Utility of 3T Lung MRI in Children with Interstitial Lung Disease

Publication date: Available online 24 November 2017
Source:Academic Radiology
Author(s): Kushaljit Singh Sodhi, Madhurima Sharma, Edward Y. Lee, Akshay Kumar Saxena, Joseph L. Mathew, Meenu Singh, Niranjan Khandelwal
Rationale and ObjectivesThe objective of this study was to assess the diagnostic utility of 3-tesla (3T) magnetic resonance imaging (MRI) of lungs in the detection of interstitial lung disease (ILD) in pediatric patients.Materials and MethodsTwelve children (mean: 8.5 years, range: 4–12 years) with ILD were consecutively enrolled in this prospective study. HRCT and 3T lung MRI were performed in all patients within 2 days of each other. The sensitivity, the specificity, the positive predictive value, and the negative predictive value of detecting lung abnormalities related to ILD with 3T lung MRI were calculated, with high-resolution computed tomography (HRCT) as a standard of reference. Agreement between HRCT and 3T lung MRI, as well as between two reviewers, was calculated with the kappa coefficient.Results3T lung MRI had low sensitivity (66.67%) and high specificity (97.33%) in the detection of abnormalities related to ILD when compared to HRCT in children. Although 3T lung MRI performed well in the detection of consolidation, parenchymal bands and fissural thickening with a sensitivity of 100%, the sensitivity of 3T lung MRI in the detection of septal thickening, ground-glass opacity, nodules, and cysts was relatively low (50.0%, 50.0%, 66.67%, and 25.0%, respectively). Substantial agreement was seen between HRCT and 3T lung MRI (k = 0.7), whereas perfect agreement was seen between two reviewers in detecting abnormalities related to pediatric ILD (k = 0.9–1.0).ConclusionsIn comparison to HRCT, 3T lung MRI with routinely available MRI protocols and sequences can also well detect abnormalities such as consolidation, parenchymal bands, and fissural thickening in children with ILD. However, evaluation of septal thickening, ground-glass opacity, nodules, and cysts is limited with 3T lung MRI.



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Non-melanoma Hutchinson's sign: A reappraisal of this important, remarkable melanoma simulant

Abstract

Background

More than 20 years ago our reappraisal of the Hutchinson Sign (HS) gave birth to the concept of the Pseudo-Hutchinson sign.

Objectives

We have found it interesting to emphasize some important histologic points and to expand the list of the numerous HS simulants.

Methods

We have examined the cutaneous samples taken from the pigmented skin of patients in association with nail matrix biopsy. We have also extended the long list of non-melanoma HS.

Results

Histologically HS may present only as an epidermal pigmentation, depending on the area sampled. Occasionally, there may be a sparse junctional melanocytic proliferation which does not demonstrate cytologic atypia due to an underlying melanocytic nevus of the nail matrix. However, early HS can show a melanoma in situ, with a HS at the proximal nail fold (PNF) and confluent atypical melanocytes in the nail matrix. Finally, involvement of the proximal nail fold, nail matrix and nail bed containing atypical melanocytes in irregular array may be seen.

Conclusion

The mere presence of periungual pigmentation is neither clinically nor histologically pathognomonic of subungual melanoma and justifies the usefulness of this work stressing the non-melanoma HS.

This article is protected by copyright. All rights reserved.

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In vivo Confocal Laser Microscopy for monitoring of actinic keratosis treatment: a comparison with histopathologic assessment after treatment with topical 5% 5-fluorouracil

Abstract

Background

Histological examination is the gold standard for actinic keratosis diagnosis; however, it is not always a feasible approach. Reflectance confocal microscopy (RCM) is a non-invasive technique that may be an alternative for monitoring actinic keratoses treatment response. Topical 5-fluorouracil is indicated for actinic keratosis multiple lesions and for field cancerization treatment.

Objectives

To assess the RCM accuracy, sensibility and specificity for actinic keratosis, considering as a gold-standard the histopathological examination; as well as to evaluate the efficacy of 5% 5-fluorouracil treatment.

Methods

This is a prospective study in actinic keratosis patients between August, 2014 and November, 2015. RCM analyses were performed in one randomly selected actinic keratosis lesion of the upper limbs by two independent observers before and after 5% 5-fluorouracil treatment. At the end of treatment and with clinical bleaching of treated lesions, histological examination was performed by two pathologists.

Results

A total of 50 lesions were enrolled, and 40 lesions presented complete clinical bleaching after treatment and were included in the final analysis. Accuracy, sensibility and specificity means among observers were 83.8%, 84.6% and 83.3%, respectively. After 5-fluorouracil treatment, actinic keratosis was diagnosed in 45.0% (observer 1) and 32.5% (observer 2) of subjects according to RCM and in 32.5% of subjects according to histological examination. Considering RCM observers diagnosis, the concordance was substantial (k 0,637, p<0,001). 5-fluorouracil led to a reduction in 55.0%-67.5% of actinic keratoses according to RCM analysis.

Conclusion

This study allows to validate of RCM as a non-invasive method capable of monitoring actinic keratosis therapeutic response to 5-fluorouracil, presenting efficacy comparable to histological examination. Additionally, the results suggest that 5-fluorouracil may be a satisfactory option for therapeutic control of this condition.

This article is protected by copyright. All rights reserved.

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Novel device-based acne treatments: comparison of a 1,450-nm diode laser and micro-needling radiofrequency on mild to moderate acne vulgaris and seborrhea in Korean patients through a 20-week prospective, randomized, split-face study

Abstract

Background

While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1,450-nm diode laser (DL) and fractional micro-needling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodeling effects.

Objective

To compare the clinical course for acne treatment between DL and FMR.

Methods

Twenty five Korean patients with mild to moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated.

Results

Both DL and FMR demonstrated steady improvement of acne and seborrhea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow up. Patients' subjective assessments for seborrhea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety proflie, no significant difference was observed between two regimens, while mild post inflammatory hyperpigmentation was observed only in DL side.

Conclusion

Both DL and FMR demonstrated efficacies for acne and seborrhea, with reasonable safety proflie. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments.

This article is protected by copyright. All rights reserved.

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Educational and Practice Gaps in the Management of Volar Melanocytic Lesions

Abstract

Background

The benign and malignant patterns of acral melanocytic nevi (AMN) and acral melanomas (AM) have been defined in a series of retrospective studies. A 3-step algorithm was developed to determine when to biopsy acral melanocytic lesions. This algorithm has only been applied to a Japanese population.

Objectives

Our study aimed to review the current management strategy of acral melanocytic lesions and to investigate the utility of the 3-step algorithm in a predominately Caucasian cohort.

Methods

A retrospective search of the pathology and image databases at Mayo Clinic was performed between the years 2006 – 2016. Only cases located on a volar surface with dermoscopic images were included. Two dermatologists reviewed all dermoscopic images and assigned a global dermoscopic pattern. Clinical and follow-up data was gathered by chart review. All lesions with known diameter and pathological diagnosis were used for the 3-step algorithm.

Results

Regular fibrillar and ridge patterns were more likely to be biopsied (p=0.01). The majority of AMN (58.1%) and AM (60%) biopsied were due to physician-deemed concerning dermoscopic patterns. 39.2% of these cases were parallel furrow, lattice-like, or regular fibrillar. When patients were asked to follow-up within a 3-6-month period, only 16.7% of the patients returned within that interval. The 3-step algorithm would have correctly identified 4/5 AM for biopsy, missing a 6mm, multi-component, invasive melanoma.

Conclusion

We found one major educational gap in the recognition of low risk lesions with high rates of biopsy of the fibrillary pattern. Recognizing low-risk dermoscopic patterns could reduce the rate of biopsy of AMN by 23.3%. We identified two major practice gaps, poor patient compliance with follow up and the potential insensitivity of the 3-step algorithm to small multi-component acral melanocytic lesions.

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Cutaneous granuloma caused by Rhizopus oryzae with a novel mutation in the CYBB gene in a monozygotic male twin

Abstract

A 2-year-old Chinese boy presented to our institution with a large lump in the sacrococcygeal region for two months, along with fever for five days. The initial lesion presented as a red papule accompanied by itching, and then progressed to 10 cm in diameter (Fig. 1a). Five days previously, the patient had developed a fever.

This article is protected by copyright. All rights reserved.

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Response to – Bullous pemphigoid inguinalis?

Abstract

We appreciate the constructive comments by author Abdelmaksoud in response to our report of bullous pemphigoid (BP) presenting in association with metastatic penile squamous cell carcinoma (SCC). Though our patient had few blisters on the back, upper limbs and oral cavity, the chief brunt of the disease was on the inguinal area. Cases of localized BP, arising after radiotherapy for breast carcinoma have been reported. Our patient developed BP before receiving radiotherapy.

This article is protected by copyright. All rights reserved.

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Bullous Pemphigoid Inguinalis?

Abstract

I read with great interest a case report by Bishnoi et al. published recently in the journal of European Academy of Dermatology and Venereology. The authors presented a case of a 43-year old man who had history of penile SCC, presented with bullous pemphigoid (BP) lesions. Interestingly, the BP lesion was limited to the inguinal region, suprapubic area and inner aspect of the right thigh, that was predominantly on top of the bilateral metastatic inguinal lymphadenopathy(LN).

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Electrochemotherapy of unresectable cutaneous tumors with reduced dosages of intravenous bleomycin: analysis of 57 patients from the InspECT (International network for sharing practices of ElectroChemoTherapy) registry

Abstract

Background

Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumors of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable in order to ameliorate ECT safety profile.

Objective

The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages.

Methods

In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7.500, 10.000, or 13.500 IU/m², instead of the standard dose of 15.000 IU/m²). Tumor response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin.

Results

We identified 57 patients with 147 tumors (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%, Kaposi sarcoma 7%, other histotypes, 7.1%. Per-tumor complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side effect (n=22 patients [39%], mostly mild; 2 patients experienced flu-like symptoms, 1 patient nausea. We observed the same CR rate (55%) in melanoma patients treated by reduced or conventional bleomycin dosages (p=1.00).

Conclusions

ECT performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.

This article is protected by copyright. All rights reserved.

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Does obesity cause a distinct phenotype of hidradenitis suppurativa?

Abstract

I have read the article by Theut Riis et al proposing BMI based clinical subtypes of hidradenitis suppurativa (HS) patients with interest. In addition to giving valuable clinical information, the article is important in the discussion of the pathophysiology of such HS subgroups, with focus on the obese subtype. The papers main difference from earlier clinical proposals of subtyping is the focus on the body mass index (BMI) as a functional factor in the disease evolution.

This article is protected by copyright. All rights reserved.

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Responsible Radiomics Research for Faster Clinical Translation

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Glioma survival prediction with the combined analysis of in vivo 11C-MET-PET, ex vivo and patient features by supervised machine learning

Gliomas are the most common types of tumors in the brain. While the definite diagnosis is routinely made ex vivo by histopathologic and molecular examination, diagnostic work-up of patients with suspected glioma is mainly done by using magnetic resonance imaging (MRI). Nevertheless, L-S-methyl-¹¹C-methionine (¹¹C-MET) Positron Emission Tomography (PET) holds a great potential in characterization of gliomas. The aim of this study was to establish machine learning (ML) driven survival models for glioma built on ¹¹C-MET-PET, ex vivo and patient characteristics. Methods: 70 patients with a treatment naïve glioma, who had a positive ¹¹C-MET-PET and histopathology-derived ex vivo feature extraction, such as World Health Organization (WHO) 2007 tumor grade, histology and isocitrate dehydrogenase (IDH1-R132H) mutation status were included. The ¹¹C-MET-positive primary tumors were delineated semi-automatically on PET images followed by the feature extraction of tumor-to-background ratio based general and higher-order textural features by applying five different binning approaches. In vivo and ex vivo features, as well as patient characteristics (age, weight, height, body-mass-index, Karnofsky-score) were merged to characterize the tumors. Machine learning approaches were utilized to identify relevant in vivo, ex vivo and patient features and their relative weights for 36 months survival prediction. The resulting feature weights were used to establish three predictive models per binning configuration based on a combination of: in vivo/ex vivo and clinical patient information (M36IEP), in vivo and patient-only information (M36IP), and in vivo only (M36I). In addition a binning-independent ex vivo and patient-only (M36EP) model was created. The established models were validated in a Monte Carlo (MC) cross-validation scheme. Results: Most prominent ML-selected and -weighted features were patient and ex vivo based followed by in vivo features. The highest area under the curve (AUC) values of our models as revealed by the MC cross-validation were: 0.9 (M36IEP), 0.87 (M36EP), 0.77 (M36IP) and 0.72 (M36I). Conclusion: Survival prediction of glioma patients based on amino acid PET using computer-supported predictive models based on in vivo, ex vivo and patient features is highly accurate.

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Model of intraperitoneal targeted alpha-particle therapy shows post-therapy cold antibody boost (PT-CAB) enhances microtumor radiation dose and treatable tumor sizes

Intraperitoneally (i.p.) administered radiolabeled monoclonal antibodies have been tested in several clinical trials, often with promising results, but never proven curative. Methods: We have previously presented simulations of clinically relevant amounts of i.p. ⁹⁰Y-mAb treatments of minimal disease and shown that such treatments are unlikely to eradicate microtumors. Our previous model simulated the kinetics of intraperitoneally infused radiolabeled mAb in man, and showed the benefit of instead using alpha-emitters such as ²¹¹At. In the current work, we introduce also penetration of mAbs into tissue of microtumors with radii up to 400 μm. Calculations were performed by dynamic simulation using the software STELLA. In order to determine the radiation dose distribution in non-vascularized microtumors of various sizes following i.p. [²¹¹At] α-RIT an in-house developed Monte Carlo program was used for microdosimetry. Our aim was to find methods that optimize the therapy for as large tumor size interval as possible. Results: Our results show that high-specific-activity radiolabeled mAbs that are bound to a tumor surface will penetrate slowly compared to the half-lives of ²¹¹At and shorter-lived radionuclides. Inner-core cells of tumors with radii >100 μm may therefore not be sufficiently irradiated. For lower specific activities, the penetration rate and the dose distribution will be more favorable for such tumors, but the dose to smaller microtumors and single cells will be low. Conclusion: Our calculations show that addition of a boost with unlabeled mAb 1–5 hours following therapy results in sufficient absorbed doses to both single cells and throughout microtumors up to ~300 μm radius. This should be valid also for other high-affinity mAbs and short-lived alpha-emitters.

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Validation of Non-Invasive Tracer Kinetic Analysis of 18F-Florbetaben PET Using a Dual Time-Window Acquisition Protocol

Accurate amyloid PET quantification is necessary for monitoring amyloid-beta accumulation and response to therapy. Currently, most of the studies are analyzed using the static standardized uptake value ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were: (1) to validate a non-invasive kinetic modeling approach for ¹⁸F-florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and (2) to assess the impact of CBF changes and radiotracer clearance on SUVRs and non-invasive kinetic modeling data in ¹⁸F-florbetaben PET. Methods: Data from twenty subjects (10 patients with probable Alzheimer's dementia/ 10 healthy volunteers) were used to compare the binding potential (BP_ND) obtained from the full kinetic analysis to the SUVR and to non-invasive tracer kinetic methods (simplified reference tissue model (SRTM), and multilinear reference tissue model 2 (MRTM2)). Different approaches using shortened or interrupted acquisitions were compared to the results of the full acquisition (0-140 min). Simulations were carried out to assess the effect of CBF and radiotracer clearance changes on SUVRs and non-invasive kinetic modeling outputs. Results: A 0-30 and 120-140 min dual time-window acquisition protocol using appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BP_ND obtained using full and dual time-window (2TW) acquisition protocols (BP_ND,2TW=0.01+ 1.00 BP_ND,FULL, R2=0.97 (MRTM2); BP_ND,2TW= 0.05+ 0.92·BP_ND,FULL, R2=0.93 (SRTM)). Simulations showed a limited impact of CBF and radiotracer clearance changes on MRTM parameters and SUVRs. Conclusion: This study demonstrates accurate non-invasive kinetic modeling of ¹⁸F-florbetaben PET data using a dual time-window acquisition protocol, thus providing a good compromise between quantification accuracy, scan duration and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-beta load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which a maximum quantification accuracy is desired, this non-invasive dual time-window acquisition protocol and kinetic analysis is recommended.

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Molecular Imaging of ABCB1/ABCG2 Inhibition at the Human Blood Brain Barrier using Elacridar and 11C-Erlotinib PET

Transporters such as ABCB1 and ABCG2 limit the exposure of several anti-cancer drugs to the brain, leading to suboptimal treatment in the central nervous system. The purpose of this study was to investigate the effects of the ABCB1/ABCG2 inhibitor elacridar on erlotinib brain uptake using ¹¹C-erlotinib PET. Methods: Elacridar and cold erlotinib were administered orally to wild type (WT) and Abcb1a/b;Abcg2 knockout mice. In addition, brain uptake was measured using ¹¹C-erlotinib imaging and ex vivo scintillation counting in knockout and WT mice. Six patients with advanced solid tumors underwent ¹¹C-erlotinib PET scans before and after a 1000 mg dose of elacridar. ¹¹C-erlotinib brain uptake was quantified by pharmacokinetic modeling using volume of distribution (VT) as outcome parameter. In addition, ¹⁵O-H2O scans were acquired prior to each ¹¹C-erlotinib scan, to measure cerebral blood flow . Results: Brain uptake of ¹¹C-erlotinib was 2.6-fold higher in Abcb1a/b;Abcg2 knockout mice than in WT mice, measured as % of injected dose/gram tissue (P = 0.01). In WT mice, addition of elacridar (at systemic plasma concentrations of ≥200 ng/mL) resulted in increased brain concentration of erlotinib, without affecting erlotinib plasma concentration. In patients, VT of ¹¹C-erlotinib did not increase after intake of elacridar (0.213±0.12 versus 0.205±0.07, P = 0.91). ¹⁵O-H2O PET showed no significant changes in cerebral blood flow. Elacridar exposure in patients was 401±154 ng/mL. No increase in VT with increased elacridar plasma exposure was found over the 271–619 ng/mL range. Conclusion: When Abcb1 and Abcg2 were disrupted in mice, brain uptake increased both at a tracer and pharmacological erlotinib dose. In patients, brain uptake of ¹¹C-erlotinib was not higher after administration of elacridar. The more pronounced role that ABCG2 appears to play at the human blood-brain barrier and the lower potency of elacridar to inhibit ABCG2 may be an explanation of these inter-species differences.

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PRDM14 directly interacts with heat shock proteins HSP90α and GRP78

Abstract

PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 needs to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer cells (TNBCs), which do not express the three most common types of receptors (estrogen receptors, progesterone receptors, and HER2). We obtained thirteen candidates that were pulled down with PRDM14 in TNBC HCC1937 and identified them by mass spectrometry. Two candidates - glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α) – were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance (SPR) analysis using GST-PRDM14 revealed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24^-CD44⁺ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggested HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.

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Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010)

Abstract

This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5,192 children with cancer (age 0-14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993-2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumours, hepatic tumours, neuroblastoma, and acute myeloid leukaemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumours, soft tissue sarcomas, malignant bone tumours, and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening programme for neuroblastoma. The large improvement in survival from CML coincided with the introduction of effective therapy (imatinib).

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Daily inspiratory muscle training lowers blood pressure and vascular resistance in healthy men and women

Abstract

Previous work has shown inspiratory muscle training (IMT) lowers blood pressure after just six weeks, identifying IMT as a potential therapeutic to prevent/treat hypertension. Here, we explore the effects of IMT on respiratory muscle strength and select cardiovascular parameters in recreationally active men and women. Subjects were randomly assigned to IMT (n = 12, 75% maximal inspiratory pressure) or sham training (n = 13, 15% maximum inspiratory pressure) groups and underwent a 6-week intervention comprising 30 breaths day⁻¹, 5 days week⁻¹. Pre- and post- training measures included maximal inspiratory pressure, and resting measures of blood pressure, cardiac output, heart rate, spontaneous cardiac baroreflex sensitivity, and systemic vascular resistance. We evaluated psychological and sleep status via administration of the Cohen-Hoberman inventory of physical symptoms and the Epworth Sleepiness Scale. Male and female subjects in the IMT group showed declines in systolic/diastolic blood pressures (−4.3/−3.9 mmHg SBP/DBP, P < 0.025) and systemic vascular resistance (-3.5 mmHg*min L⁻¹, P = 0.008) at Week 6. There was no effect of IMT on cardiac output (P = 0.722), heart rate (P = 0.795), or spontaneous baroreflex sensitivity (P = 0.776). IMT subjects also reported fewer stress-related symptoms pre versus post training (12.5 ± 8.5 vs. 7.2 ± 9.7, P = 0.025). Based on these results, we suggest a short course of inspiratory muscle training confers significant respiratory and cardiovascular improvements and parallel (modest) psychological benefits in healthy men and women.

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On computational fluid dynamics models for sinonasal drug transport: relevance of nozzle subtraction and nasal vestibular dilation

Summary

Generating anatomically realistic three-dimensional (3D) models of the human sinonasal cavity for numerical investigations of sprayed drug transport presents a host of methodological ambiguities. For example, subject-specific radiographic images used for 3D reconstructions typically exclude spray bottles. Subtracting a bottle contour from the 3D airspace and dilating the anterior nasal vestibule for nozzle placement augment the complexity of model-building. So, we explored the question: how essential are these steps to adequately simulate nasal airflow and identify the optimal delivery conditions for intranasal sprays? In particular, we focused on particle deposition patterns in the maxillary sinus, a critical target site for chronic rhinosinusitis (CRS). The models were reconstructed from post-surgery computed tomography scans for a 39-year-old Caucasian male, with CRS history. Inspiratory airflow patterns during resting breathing are reliably tracked through CFD-based steady state laminar-viscous modeling and such regimes portray relative lack of sensitivity to inlet perturbations. Consequently, we hypothesized that the posterior airflow transport and the particle deposition trends should not be radically affected by the nozzle subtraction and vestibular dilation. The study involved 1 base model and 2 derived models; the latter two with nozzle contours (two different orientations) subtracted from the dilated anterior segment of the left vestibule. We analyzed spray transport in the left maxillary sinus for multiple release conditions. Similar release points, localized on an approximately 2mm-by-4.5mm contour, facilitated improved maxillary deposition in all three test cases. This suggests functional redundancy of nozzle insertion in a 3D numerical model for identifying the optimal spray release locations. This article is protected by copyright. All rights reserved.

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CT Imaging of Emergent Renal Conditions

The kidneys are paired intra-abdominal organs which provide essential functions and maintain homeostasis throughout the human body. Numerous disease processes affect the kidneys and cause acute renal dysfunction or other potentially catastrophic complications. These conditions can be broadly categorized into obstructive, infectious, hemorrhagic, traumatic and vascular diseases. Imaging plays a vital role in the work-up and diagnosis of acute and emergent renal conditions. Evaluation of emergent renal conditions with a focus on CT imaging are discussed.

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Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients With Laryngopharyngeal Reflux

Our study was designed to further evaluate the relationships between the saliva pepsin level and the symptoms and quality of life of patients with laryngopharyngeal reflux (LPR).

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Pin-up Glottoplasty: Feasibility Study of a Novel Approach Medializing or Lateralizing Immobile Vocal Folds

Principles in medializing and lateralizing vocal folds have not changed a lot within the last decades (Isshiki et al, 1974; Bruenings, 1911). We present a feasibility study for a completely new approach to perform medialization and lateralization of immobile vocal folds.The method was tested on 20 human larynges by inserting a 21G needle into the vocal fold, medializing (or, in other cases, lateralizing) the vocal cord and fixing the needle at the cricoid cartilage posteriorly. The anterior and posterior fixation points of the needle allow for a stable positioning of the needle, which we consider necessary in both cases of medialization or lateralization.

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A case of large cell neuroendocrine carcinoma of the uterine cervix misdiagnosed as adenocarcinoma in Thinprep cytology test

Jong-Hee Nam, Jongin Na, Nah-Ihm Kim, Ga-Eon Kim, Chang-Soo Park, Yoo-Duk Choi

CytoJournal 2017 14(1):28-28

Large cell neuroendocrine carcinoma (LCNEC) of uterine cervix is a rare malignancy with aggressive behavior and poor clinical outcome even in its early stage. Few cytopathologic features of cervical LCNEC have been reported previously. A 57-year-old postmenopausal African American female, presented to the local health department with a chief complaint of heavy vaginal bleeding. A 45-year-old female presented with 20 months of vaginal pruritus and foul odor. Cervical malignancy was suspected by pelvis magnetic resonance imaging. Thinprep cytology test demonstrated ball-like tumor cell clusters in a necrotic background. Cytologic diagnosis of adenocarcinoma was rendered. However, the histologic and immunohistochemical examination of cervical biopsy revealed the LCNEC of the uterine cervix. Due to its rarity, LCNEC may pose a diagnostic challenge in cervical cytology. Cytopathologists should pay attention to the cytological features of cervical LCNEC, such as rosettoid pattern, nuclear molding, and thin nuclear membrane for differentiation from other mimics.

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Cytokeratin 20/p53 dual immunocytochemistry for improving the diagnostic accuracy of urine liquid-based cytology in the detection of urothelial neoplasm: A retrospective study

Hyun-Jung Kim, Ji-Hyeong Yoo

CytoJournal 2017 14(1):27-27

Backgrounds: Dual immunocytochemistry (DIC) with cytokeratin (CK) 20 and p53 in liquid-based cytology is a tool for improving the accuracy of urine cytology (UC). This study was conducted to compare the diagnostic accuracy of UC alone with that of UC combined with CK20/p53 DIC. Methods: We retrieved urine samples collected between January 2015 and March 2016 stored in PreservCyt®solution that were from cases categorized as malignant, highly suspicious, suspicious, and atypical and that were matched with a subsequent biopsy. We re-prepared 63 samples of 28 patients for DIC and blindly evaluated 63 pairs of original Papanicolaou smears and DIC. Results: Of the 63 samples, 11 could not be analyzed because of the low number of atypical urothelial cells, and the results of the remaining 52 samples were as follows: 34 positive and 18 negative. The positive predictive value of DIC was 100%, and the negative predictive value was 78%. Fifteen DIC-positive cases, histologically proven as malignant were originally diagnosed as highly suspicious (4), suspicious (8), and atypical (3), which were strongly suggestive of "urothelial carcinoma". Four negative cases, histologically confirmed as non-neoplastic cases, were filtered from false positivity. Conclusions: Despite the small sample size, this study demonstrated the diagnostic utility, high sensitivity, and positive predictive value of CK20/p53 DIC, especially in cases with a small number of single malignant cells or cellular clusters of reactive atypical urothelial cells. Thus, CK20/p53 DIC can be used for improving diagnostic accuracy of UC, either as an ancillary method to cytology or as a part of a potential future diagnostic panel to improve patient diagnosis and management.

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Dysregulatory effects of retinoic acid isomers in late zebrafish embryos

Abstract

All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural derivatives of vitamin A that contribute to the normal vertebrate development by affecting gene expression through the retinoic acid signalling pathway. We show transcriptomic effects of the ectopic addition of atRA or 9cRA to zebrafish embryos at the posthatching embryonic stage. Exposure for 24 or 72 h to sublethal concentrations of both isomers resulted in characteristic transcriptome changes, in which many proliferation and development-related genes became underexpressed, whereas genes related to retinoid metabolism and some metabolic functions became overrepresented. While short and long exposures elicit essentially the same set of genes, atRA specifically induced expression of a specific subset of proteases, likely acting at the extracellular level, and of elements of the response to xenobiotics. These results reflect the well-known antiproliferative activity of retinoids, and they suggest a dysregulation of the developmental process at final stages of embryogenesis. They also indicate a potential role of endopeptidases as markers of developmental alterations, as well as their possible control by the retinoic signalling pathway. We propose to monitor mRNA levels of cyp16a, cyp16b, and cyp16c in zebrafish embryos as a bioassay for retinoid disruption.

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Volatile organic compounds and nitric oxide as responses of a Brazilian tropical species to ozone: the emission profile of young and mature leaves

Abstract

The emission profile of volatile organic compounds (VOCs) and nitric oxide (NO) in young and mature leaves of Croton floribundus was assessed in plants exposed to filtered air (FA) and ozone-enriched filtered air (FA+O₃). After the period of exposure, leaves were enclosed in polyethylene terephthalate bags and VOCs were collected in young and mature leaves. Both young and mature leaves constitutively emitted the same VOC, but the concentrations were higher in young leaves. O₃ exposure induced the emission of sesquiterpenes (mainly β-caryophyllene) known as antioxidant compounds that may scavenge O₃. Young leaves were the highest emitters of sesquiterpenes. O₃ induced a rapid accumulation of NO in different tissues and leaf developmental stages; this accumulation was marked in palisade and spongy parenchyma cells in young and mature leaves, respectively. O₃ altered the levels of the signaling compound methyl salicylate (MeSA). Moreover, our data showed that NO together with VOC emissions, such as geranyl acetate, α-cadiene, trans-farnesol, cis-β-farnesene, and MeSA, participate of plant defense mechanisms against the oxidative damage caused by O₃.

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Enhanced phosphorus removal using acid-treated magnesium slag particles

Abstract

Magnesium-enriched magnesium slag particles (MSPs) can be used as an adsorption substrate as well as the magnesium source for struvite precipitation. In this study, an HCl treatment was used to enhance MSPs for phosphorus removal. After soaking in 1 mol/L HCl, an 11.27% decrease in median diameter (D50) and a 6.73% increase in specific surface area were observed when compared with the original MSPs. The improvement of the MSP surface properties resulted in 188.96 mg/kg increase in the PO₄³⁻ adsorption capacity. Irrespective of HCl treatment, the phosphorus adsorption process followed the Dubinin–Radushkevich (D–R) model much more accurately than the Langmuir and Freundlich equations with correlation coefficients higher than 0.94. The adsorption free energy obtained through the D–R model revealed a 9.75% decrease after HCl treatment. Sequential fraction extraction results indicated that 96% of the Mg²⁺ released from the HCl-treated MSPs came from acid-soluble magnesium (exchangeable and carbonate-bound). Mg²⁺ obtained from HCl-treated solutions provided a reliable magnesium source for struvite precipitation. The PO₄³⁻ removal rate can reach 53.63% with the optimal pH value of 10.0 and molar ratio of NH₄⁺ to PO₄³⁻ of 1:1. Struvite precipitation and adsorption can simultaneously occur in HCl-treated MSP solution. It contributed 63.19% to the overall PO₄³⁻ removal and is a major contributor compared with adsorption. Thus, HCl treatment greatly enhanced the potential of MSPs for phosphorus removal due to an improved adsorption capacity and is a reliable Mg²⁺ source for struvite precipitation.

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PCDD/PCDF formation in the chlor-alkali process—laboratory study and comparison with patterns from contaminated sites

Abstract

Studies on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) during the electrolysis of sodium chloride solution (brine) using graphite or titanium electrodes were carried out at a laboratory scale. High concentrations of PCDFs but no PCDDs were formed in tests using graphite electrodes. With titanium electrodes, PCDFs were only formed when tar pitch was added and mainly originated from the dibenzofuran present in the tar. For the first time, a detailed assessment of the formation of mono- to octachlorinated PCDD/PCDF from tar pitch was investigated. The assessment included of the chlorination steps proved that PCDFs were formed by successive lateral chlorinated from dibenzofuran to MonoCDFs, DiCDFs, and TriCDFs to form the typical known "chlorine pattern" of TetraCDF to OctaCDF with a dominance of 1,2,7,8- and 2,3,7,8-TetraCDFs, 1,2,3,7,8-PentaCDF, and 1,2,3,4,7,8-HexaCDF as marker congeners. The final homologue distributions depended on reaction time and reaction temperature. In addition, electrolysis with non-chlorinated dibenzo-p-dioxins, dibenzofuran, and biphenyl was carried out. As a result, PCDDs, PCDFs, and PCB were formed at comparable yields. Congener patterns in soil samples from a PCDD/F-contaminated site where chlor-alkali electrolysis had been operated for decades in Japan had identical isomer distribution demonstrating the source and contamination potential and risk of these processes. Therefore, sites where in the past 120 years chlor-alkali electrolysis has been operated or where residues from chlor-alkali production or other chlorine using industries have been disposed should be assessed for their pollution level and exposure relevance. The assessment of total organohalogen content revealed that PCDF is only a small fraction of organohalogens in the contaminated soils. For an appropriate risk assessment, also other chlorinated aromatic compounds such as PCBs or PCNs need to be considered.

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Dimensions of hard and soft tissue around adjacent, compared with single-tooth, zirconia implants

Preservation or regeneration of the papilla has always been a challenge around consecutive implants or with implants next to teeth, and many studies have evaluated the papilla's behaviour and patterns based on surgical technique and prosthetic design, though evidence about its behaviour around zirconia implants is scarce. The aim of this study was to evaluate papilla behaviour between implants and teeth (tooth-implant group) and between consecutive implants (implant–implant group). Ninety patients with 122 zirconia implants (Straumann® PURE Ceramic Implant) were examined at the one-year follow up.

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