Extended Chest Wall Based Flap and Lipofilling for Immediate Breast Reconstruction for Obese Patients

Publication date: Available online 9 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Maria Cecilia Closs Ono, Ruth Maria Graf, Dayane Raquel de Paula, Fabiola Grigoletto Lupion, Renato da Silva Freitas

Percutaneous transluminal plasty: a novel approach for refractory anastomotic stricture after esophagectomy

Abstract

Anastomotic stricture is often observed after esophagectomy. Surgical treatment is considered for refractory stricture to conservative treatments. However, it is not established what type of surgery is safe and effective. In this report, we present a novel approach, percutaneous transluminal plasty, for refractory anastomotic stricture reconstructed via the subcutaneous route in esophagectomy. We believe that the effectiveness and safety of this technique is considerably good and can become a good alternative for refractory stricture after esophagectomy.

Sífilis maligna, una presentación de sífilis a tener en cuenta

Publication date: Available online 8 August 2018

Source: Actas Dermo-Sifiliográficas

Author(s): X. Fustà-Novell, D. Morgado-Carrasco, A. Barreiro-Capurro, C. Manzardo, M. Alsina-Gibert, Miembros del Grupo de Trabajo de Infecciones de Transmisión Sexual del Hospital Clínic de Barcelona, Irene Fuertes-de Vega, José-Luís Blanco, Anna González, Asunción Moreno, Miriam Álvarez, Jordi Bosch

Resumen

La sífilis maligna es una forma infrecuente de sífilis secundaria asociada a la infección por el VIH, caracterizada clínicamente por nódulos necróticos y lesiones ulceradas generalizadas. Presentamos 4 pacientes diagnosticados de sífilis maligna tras revisar los casos de sífilis diagnosticados en nuestro centro entre 2012 y 2016. Describimos los aspectos epidemiológicos, clínicos, histopatológicos y serológicos, así como su relación con el VIH y la respuesta al tratamiento. Aunque se trate de una forma de sífilis poco frecuente, en los últimos años ha aumentado el número de casos publicados, principalmente pacientes jóvenes infectados por el VIH. Es necesario incluir la sífilis maligna en el diagnóstico diferencial de pacientes infectados por el VIH con lesiones ulceradas y necróticas.

Abstract

Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions.

Graphical abstract

Autologous Fat Grafting after Sarcoma surgery: evaluation of oncological safety

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Angela Pennati, Egidio Riggio, Giuseppe Marano, Elia Biganzoli

Abstract

Background

The regenerative effectiveness of lipoaspirate procedures relies on the presence of mesenchymal stem cells, but the stromal microenvironment and hormonal secretions of adipose tissue can be involved in cancer growth. Only few oncological outcome studies of fat grafting at the surgical site of malignant neoplasms of mesenchymal origin are available; none of these examined a series of sarcoma cases.

Objectives

We analyzed outcome in terms of local or distant spread and overall survival in order to investigate the oncological safety of fat grafting in sarcoma patients.

Patients and methods

Sixty consecutive patients who had undergone 143 fat grafting procedures after surgical resection of bone and soft tissue sarcomas of the head, trunk and limbs with clear resection margins were enrolled from 2004 to 2015 in our tertiary care center. A multidisciplinary sarcoma team administered adjuvant therapies. Patients were recurrence free at fat grafting.

Results

The overall median follow-up was 7.5 years. At follow-up after fat grafting (2.4 years), one patient had distant metastasis and two had local relapse. Kaplan-Meier analysis showed disease-free survival of 95.4% (CI:89.1-100.0) at 24 months. The risk of local recurrence within 24 months was 4.6% (CI:0.0-20.9). The probability of not having local recurrence after fat grafting was ≥89.1%.

Conclusion

We found no evidence of an increased cancer risk after fat grafting procedures in sarcoma patients, but a stimulatory role of fat cannot be excluded for bone sarcomas based on the cases reported here and further studies are therefore needed.

Half-transection Method Combined with Intravascular Stent for Supermicrosurgical Lymphaticovenular Anastomosis

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Wang Jing, Mitsunaga Narushima

The impact of surgical alar (lower lateral) cartilage manipulation on lateral crural stiffness

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Kathak Vachhani, Pierre Lapaine, Saeid Samiezadeh, Cari M. Whyne, Jeffrey A. Fialkov

Abstract

Background

Cephalic trimming of the alar (or lower lateral) cartilage may cause weakening leading to external nasal valve collapse. Numerous methods have been proposed to combat this weakening in order to maintain lateral crural stiffness. The purpose of this study was to quantify the effect of mucosal stripping, cephalic trimming, cephalic turn-in flap, and lateral crural strut grafting on lateral crural stiffness.

Methods

In situ cyclic compressive loading was performed on eight lateral crura in 4 fresh frozen cadaveric specimens. Testing was performed on the unaltered degloved cartilage (intact) and following each of the following interventions: mucosal stripping, cephalic turn-in flap, cephalic trimming, and lateral crural strut grafting. Linear regression of the generated force-displacement curves was used to calculate stiffness. Each intervention was compared to the intact cartilage.

Results

Alar cartilage of all of the specimens demonstrated a linear response to compressive loading. Intact cartilage had a mean stiffness of 3.53 N/mm. Mucosal stripping and cephalic turn-in flaps yielded similar stiffness values to intact cartilage. Cephalic trimming reduced stiffness in all cases by a mean of 1.09 N/mm (p = 0.003). Lateral crural strut grafting significantly increased stiffness by a mean of 3.67 N/mm (p = 0.0001).

Conclusions

Cephalic trimming leads to decreased lateral crural stiffness in cadaveric specimens. Cephalic turn-in flaps restore pre-trimmed stiffness, and lateral crural strut grafting increases overall stiffness of the cartilage. These findings should be considered in patients undergoing rhinoplasty, particularly if there are concerns regarding potential external valve collapse.

“Hand rejuvenation by Stromal Enriched Lipograft”

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Aris Sterodimas, Filippo Boriani, Beatriz Nicaretta, Luiz Haroldo Pereira

Skin Perforator Mapping Method for Anterolateral Thigh Flap using Indocyanine Green Angiography

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Ryohei Ishiura, Minami Fujita, Megumi Furuya, Chihena Banda, Mitsunaga Narushima

Potential of performing a microvascular free flap reconstruction using solely a 3D Exoscope instead of a conventional microscope

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Andrzej A. Piatkowski, Xavier H.A. Keuter, Rutger M. Schols, René R.W.J. van der Hulst

New technical method to correct secondary vermilion deformities with cleft lip

Publication date: Available online 8 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Takatoshi Yotsuyanagi, Ken Yamashita, Makoto Yamauchi, Asuka Sugai, Shinji Kato, Ayako Gonda, Arisa Kita, Ayaka Kitada

Summary

Various techniques for correcting whistling deformities that occurred after primary surgery for cleft lip have been reported. These techniques are mainly intended to correct the lack of volume of the red lip. However, irregularity of the dry-wet lip junction (mucocutaneous junction) in the red lip has rarely been mentioned. If the wet lip is located in an exposed area, not only is the aesthetic appearance poor but also uncomfortable complications such as a crusted or bleeding lip repeatedly occur under a dry condition.

A new technique for correcting the irregular line of the dry-wet lip junction is described in this report. The technique is simple. After removal of the exposed wet lip, flaps are designed on both dry lip sides of the defect as M-W-M plasty and are transposed toward the defect. The dog-ears are small, the scar is inconspicuous because it is incorporated with the wrinkle line, and scar contracture is prevented. In addition, more soft tissues may be included to correct a mild whistling deformity.

Stability of mercury on a novel mineral sulfide sorbent used for efficient mercury removal from coal combustion flue gas

Abstract

Nano-structured zinc sulfide (Nano-ZnS) has been demonstrated to be a promising alternative to activated carbon (AC) for controlling mercury emission from coal combustion flue gas. The ultimate fate of the mercury-laden Nano-ZnS after mercury capture is mostly disposed in landfill with fly ashes. Thus, the stability of mercury adsorbed on the Nano-ZnS is of considerable significance in the secured disposal of fly ash after mercury removal and in the commercial application of the Nano-ZnS sorbent for removal of mercury from coal combustion flue gas. In this work, a modified toxicity characteristic leaching procedure (TCLP) was conducted to evaluate the leachability of mercury on the Nano-ZnS. The effects of leachate pH value, leaching time, liquid-to-solid ratio, and acid rain types on mercury leaching from the mercury-laden Nano-ZnS were systematically investigated. The TCLP results show that the concentration of mercury in leachate was far below the safe limit (200 μg/L) as imposed by the US Environmental Protection Agency (EPA) for classifying a material as a hazardous waste. All the key parameters that generally affected metal leaching rate exhibited slight effect on mercury leaching from the mercury-laden Nano-ZnS. Leaching tests at various highly severe conditions resulted in less than 0.01% mercury leaching from the mercury-laden Nano-ZnS. Sequential selective extraction tests demonstrated that mercury sulfide (HgS) was the dominant adsorption product on the Nano-ZnS, which guaranteed the excellent stability of mercury adsorbed on the Nano-ZnS.

Graphic abstract

ᅟ

Waste-cleaning waste: synthesis of ZnO porous nano-sheets from batteries for dye degradation

Abstract

This paper describes a clean approach of waste-cleaning waste. Two-dimensional (2D) ZnO porous nano-sheets were synthesized from end-of-life zinc-carbon batteries via a simple homogeneous precipitation-calcination route, and the as-synthesized product was applied as photocatalyst for the purpose of photodegradation of methylene blue/MB aqueous solution under UV-Vis irradiation. Precipitation at ambient temperature resulted in the formation of the crystalline phase of zinc hydroxide nitrate hydrate [Zn₅(OH)₈(NO₃)₂(H₂O)₂], which was then transformed to ZnO through calcination. FE-SEM studies revealed the resulting ZnO had the morphology of porous nano-sheets with thickness of up to 100 nm. The photocatalytic activity tests proved that the batteries-derived ZnO porous nano-sheets can be a promising candidate for photodegradation of organic pollutant in industrial waste water. The results presented here confirm a possibility of utilization waste batteries as a resource of photodegrading MB in wastewater treatment, hereby an opportunity to deliver environmental benefits.

Graphical abstract

The effect of levamisole in the treatment of recalcitrant recurrent erythema multiforme major: An observational study

Erythema multiforme major (EMM) is an immune-mediated mucocutaneous eruption characterized by distinctive cutaneous target lesions with variable mucosal involvement. EMM is usually triggered by herpes simplex virus (HSV), Mycoplasma pneumoniae (M. pneumoniae), or other infections. Reactivation or reinfection of HSV accounts for more than 70% of cases of recurrent EMM. Although the majority of patients have a benign clinical course, more than 30% of patients suffer from frequent recurrences of EMM over years, leading to substantial morbidity [1,2].

Amylose cutanée dychromique autosomique récessive et mutations de GPNMB

Publication date: Available online 8 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): O. Dereure

Efficacy and safety data for checkpoint inhibitors in advanced melanoma under real-life conditions: A monocentric study conducted in Nice from 2010 to 2016

Publication date: Available online 8 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): H. Taquin, E. Fontas, O. Massol, P. Chevallier, R. Balloti, G. Beranger, J.-P. Lacour, T. Passeron, H. Montaudié

Summary

Background

Immunotherapies using anti-CTLA4 and anti-PD1 antibodies have revolutionised the management of patients with advanced melanoma. The aim of our study was to analyse the efficacy and safety of immunotherapies in patients with advanced melanoma under real-life conditions.

Methods

We conducted a monocentric, retrospective, observational study that included all patients treated with immunotherapies (ipilimumab, i.e. ipi; nivolumab, i.e. niv and pembrolizumab, i.e. pbr) for advanced melanoma with exclusion of primary mucosal or ocular melanoma. The primary endpoint was progression-free survival (PFS).

Results

A total of 110 patients were included. Median PFS was better in the anti-PD1 group than in the anti-CTLA4 group (3.9 months vs. 2.9 months, P = 0.025). The frequency of adverse events of any grade was 53.4% with ipi, 66.7% with niv and 75% with pbr.

Discussion

Our study shows slightly inferior efficacy data vs. clinical trials of ipi and niv because patients were presenting more severe illness at inclusion. Nevertheless, the study argues in favour of the superiority of anti-PD1 antibodies vs. anti-CTLA4 antibodies in terms of PFS and best overall response. Moreover, our study exhibits safety data comparable to those from clinical trials except for a lower frequency with ipi.

Conclusion

Our efficacy and safety data obtained under real-life conditions are reassuring since they are consistent with data already published.

Résumé

Introduction

Les immunothérapies par anti-CTLA4 et anti-PD1 ont révolutionné la prise en charge du mélanome avancé. Le but de ce travail était d'étudier l'efficacité et la tolérance des immunothérapies utilisées en conditions de vie réelle chez des patients traités pour un mélanome avancé.

Méthodes

Étude observationnelle, rétrospective, monocentrique, incluant les patients en immunothérapie par ipilimumab (ipi), nivolumab (ni) ou pembrolizumab (pbr) pour un mélanome avancé hors mélanome muqueux ou choroïdien. Le critère principal de jugement était la survie sans progression (SSP).

Résultats

Au total, 110 patients ont été inclus. La médiane de SSP des patients sous anti-PD1 était supérieure à celle des patients traités par anti-CTLA4 (3,9 mois vs. 2,9 mois ; p = 0,025). La fréquence de survenue d'évènements indésirables quel que soit leur grade était de 53,4 % pour l'ipi, 66,7 % pour le niv et 75 % pour le pbr.

Discussion

Notre étude montre des données d'efficacité légèrement inférieures à celles des essais cliniques pour l'ipi et le niv, en lien avec des patients plus sévères à l'inclusion. Néanmoins, notre travail est en faveur de la supériorité des anti-PD1 par rapport à l'anti-CTLA4 en termes de SSP et de meilleure réponse globale. Il objective enfin des données de tolérance comparables à celles des essais cliniques, mis à part une fréquence moindre d'évènements indésirables dans the ipi group.

Conclusion

Nos données d'efficacité et de tolérance des immunothérapies dans le mélanome avancé en vie réelle sont rassurantes car cohérentes avec les données de la littérature.

Skin Perforator Mapping Method for Anterolateral Thigh Flap using Indocyanine Green Angiography

Anterolateral thigh flap is one of the most popular flaps among microsurgeons. This flap was born in 19841), however it is still being refined to date 2, 3). In developing the flap, skin perforator mapping plays an important role in improving the reliability of operations. Nowadays, several methods of detecting perforators are reported. Among these, CT angiography, Sound Doppler and Color Doppler are the standard used to locate perforators.

Autologous Fat Grafting after Sarcoma surgery: evaluation of oncological safety

The regenerative effectiveness of lipoaspirate procedures relies on the presence of mesenchymal stem cells, but the stromal microenvironment and hormonal secretions of adipose tissue can be involved in cancer growth. Only few oncological outcome studies of fat grafting at the surgical site of malignant neoplasms of mesenchymal origin are available; none of these examined a series of sarcoma cases.

Potential of performing a microvascular free flap reconstruction using solely a 3D Exoscope instead of a conventional microscope

Since the introduction of the operating microscope in the mid of the 20th century reconstructive microsurgery has emerged and pushed its boundaries continuously 1, 2.

“Hand rejuvenation by Stromal Enriched Lipograft”

The rejuvenation of the hand has received increased attention recently. Autologous transplantation of fat tissue enables subcutaneous regeneration by refilling the subcutaneous space 1,2 and hence reducing some of the age-related degenerative processes of the hand dorsum such as epidermal changes, dermal and subdermal atrophy, with deep intermetacarpal spaces, prominent bones and tendons, and bulging reticular veins.

Extended Chest Wall Based Flap and Lipofilling for Immediate Breast Reconstruction for Obese Patients

Increasing rates of obesity in the general population have coincided with increased rates of obese patients with breast cancer1. Breast reconstruction in the overweight population represents a challenge for the plastic surgeon. Multiple studies have shown very high complication rates for both prosthetic and autologous reconstruction in these patients. Obesity confers independent risk of perioperative medical and surgical morbidity in breast reconstruction population2.

The impact of surgical alar (lower lateral) cartilage manipulation on lateral crural stiffness

Cephalic trimming of the alar (or lower lateral) cartilage may cause weakening leading to external nasal valve collapse. Numerous methods have been proposed to combat this weakening in order to maintain lateral crural stiffness. The purpose of this study was to quantify the effect of mucosal stripping, cephalic trimming, cephalic turn-in flap, and lateral crural strut grafting on lateral crural stiffness.

New technical method to correct secondary vermilion deformities with cleft lip

Various techniques for correcting whistling deformities that occurred after primary surgery for cleft lip have been reported. These techniques are mainly intended to correct the lack of volume of the red lip. However, irregularity of the dry-wet lip junction (mucocutaneous junction) in the red lip has rarely been mentioned. If the wet lip is located in an exposed area, not only is the aesthetic appearance poor but also uncomfortable complications such as a crusted or bleeding lip repeatedly occur under a dry condition.

Half-transection Method Combined with Intravascular Stent for Supermicrosurgical Lymphaticovenular Anastomosis

Since the revolution of supermicrosurgical technique was first published in 2000 as the least invasive treatment for lymphedema, lymphaticovenular anastomosis (LVA) has become popular for the treatment of lymphedema and has been proved effective in reducing lymphedema severity.1-3 However, the lymphaticovenular anastomosis is a demanding technique because the functioning drainage lymphatic vessel is translucent, soft and has a thin wall. To overcome these challenges, the Intravascular Stent (IVaS) has been applied for safe and precise LVA.

The Transmembrane Domain of Synaptobrevin Influences Neurotransmitter Flux through Synaptic Fusion Pores

The soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins synaptobrevin (Syb), syntaxin, and SNAP-25 function in Ca²⁺-triggered exocytosis in both endocrine cells and neurons. The transmembrane domains (TMDs) of Syb and syntaxin span the vesicle and plasma membrane, respectively, and influence flux through fusion pores in endocrine cells as well as fusion pores formed during SNARE-mediated fusion of reconstituted membranes. These results support a model for exocytosis in which SNARE TMDs form the initial fusion pore. The present study sought to test this model in synaptic terminals. Patch-clamp recordings of miniature EPSCs (mEPSCs) were used to probe fusion pore properties in cultured hippocampal neurons from mice of both sexes. Mutants harboring tryptophan at four different sites in the Syb TMD reduced the rate-of-rise of mEPSCs. A computer model that simulates glutamate diffusion and receptor activation kinetics could account for this reduction in mEPSC rise rate by slowing the flux of glutamate through synaptic fusion pores. TMD mutations introducing positive charge also reduced the mEPSC rise rate, but negatively charged residues and glycine, which should have done the opposite, had no effect. The sensitivity of mEPSCs to pharmacological blockade of receptor desensitization was enhanced by a mutation that slowed the mEPSC rate-of-rise, suggesting that the mutation prolonged the residence of glutamate in the synaptic cleft. The same four Syb TMD residues found here to influence synaptic release were found previously to influence endocrine release, leading us to propose that a similar TMD-lined fusion pore functions widely in Ca²⁺-triggered exocytosis in mammalian cells.

SIGNIFICANCE STATEMENT SNARE proteins function broadly in biological membrane fusion. Evidence from non-neuronal systems suggests that SNARE proteins initiate fusion by forming a fusion pore lined by transmembrane domains, but this model has not yet been tested in synapses. The present study addressed this question by testing mutations in the synaptic vesicle SNARE synaptobrevin for an influence on the rise rate of miniature synaptic currents. These results indicate that synaptobrevin's transmembrane domain interacts with glutamate as it passes through the fusion pore. The sites in synaptobrevin that influence this flux are identical to those shown previously to influence flux through endocrine fusion pores. Thus, SNARE transmembrane domains may function in the fusion pores of Ca²⁺-triggered exocytosis of both neurotransmitters and hormones.

Working Memory: Delay Activity, Yes! Persistent Activity? Maybe Not

Persistent spiking has been thought to underlie working memory (WM). However, virtually all of the evidence for this comes from studies that averaged spiking across time and across trials, which masks the details. On single trials, activity often occurs in sparse transient bursts. This has important computational and functional advantages. In addition, examination of more complex tasks reveals neural coding in WM is dynamic over the course of a trial. All this suggests that spiking is important for WM, but that its role is more complex than simply persistent spiking.

Dual Perspectives Companion Paper:Persistent Spiking Activity Underlies Working Memory, by Christos Constantinidis, Shintaro Funahashi, Daeyeol Lee, John D. Murray, Xue-Lian Qi, Min Wang, and Amy F.T. Arnsten

Efficient Coding in Visual Working Memory Accounts for Stimulus-Specific Variations in Recall

Recall of visual features from working memory varies in both bias and precision depending on stimulus parameters. Whereas a number of models can approximate the average distribution of recall error across target stimuli, attempts to model how error varies with the choice of target have been ad hoc. Here we adapt a neural model of working memory to provide a principled account of these stimulus-specific effects, by allowing each neuron's tuning function to vary according to the principle of efficient coding, which states that neural responses should be optimized with respect to the frequency of stimuli in nature. For orientation, this means incorporating a prior that favors cardinal over oblique orientations. While continuing to capture the changes in error distribution with set size, the resulting model accurately described stimulus-specific variations as well, better than a slot-based competitor. Efficient coding produces a repulsive bias away from cardinal orientations, a bias that ought to be sensitive to changes in the environmental statistics. We subsequently tested whether shifts in the stimulus distribution influenced response bias to uniformly sampled target orientations in human subjects (of either sex). Across adaptation blocks, we manipulated the distribution of nontarget items by sampling from a bimodal congruent (incongruent) distribution with peaks centered on cardinal (oblique) orientations. Preadaptation responses were repulsed away from the cardinal axes. However, exposure to the incongruent distribution produced systematic decreases in repulsion that persisted after adaptation. This result confirms the role of prior expectation in generating stimulus-specific effects and validates the neural framework.

SIGNIFICANCE STATEMENT Theories of neural coding have been used successfully to explain how errors in recall from working memory depend on the number of items stored. However, recall of visual features also shows stimulus-specific variation in bias and precision. Here we unify two previously unconnected theories, the neural resource model of working memory and the efficient coding framework, to provide a principled account of these stimulus-specific effects. Given the importance of working memory limitations to multiple aspects of human and animal behavior, and the recent high-profile advances in theories of efficient coding, our modeling framework provides a richer, yet parsimonious, description of how orientation encoding influences visual working memory performance.

Persistent Spiking Activity Underlies Working Memory

Persistent activity generated in the PFC during the delay period of working memory tasks represents information about stimuli held in memory and determines working memory performance. Alternative models of working memory, depending on the rhythmicity of discharges or exclusively on short-term synaptic plasticity, are inconsistent with the neurophysiological data.

Dual Perspectives Companion Paper:Working Memory: Delay Activity, Yes! Persistent Activity? Maybe Not, by Mikael Lundqvist, Pawel Herman, and Earl K. Miller

Synaptopathy in the Aging Cochlea: Characterizing Early-Neural Deficits in Auditory Temporal Envelope Processing

Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age.

SIGNIFICANCE STATEMENT Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.

Challenges in Studying Multidimensional Semantic Representations in the Human Brain

A Generic Mechanism for Perceptual Organization in the Parietal Cortex

Our visual system's ability to group visual elements into meaningful entities and to separate them from others is referred to as scene segmentation. Visual motion often provides a powerful cue for this process as parallax or coherence can inform the visual system about scene or object structure. Here we tested the hypothesis that scene segmentation by motion cues relies on a common neural substrate in the parietal cortex. We used fMRI and a set of three entirely distinct motion stimuli to examine scene segmentation in the human brain. The stimuli covered a wide range of high-level processes, including perceptual grouping, transparent motion, and depth perception. All stimuli were perceptually bistable such that percepts alternated every few seconds while the physical stimulation remained constant. The perceptual states were asymmetric, in that one reflected the default (nonsegmented) interpretation, and the other the non-default (segmented) interpretation. We confirmed behaviorally that upon stimulus presentation, the default percept was always perceived first, before perceptual alternations ensued. Imaging results showed that across all stimulus classes perceptual scene-segmentation was associated with an increase of activity in the posterior parietal cortex together with a decrease of neural signal in the early visual cortex. This pattern of activation is compatible with predictive coding models of visual perception, and suggests that parietal cortex hosts a generic mechanism for scene segmentation.

SIGNIFICANCE STATEMENT Making sense of cluttered visual scenes is crucial for everyday perception. An important cue to scene segmentation is visual motion: slight movements of scene elements give away which elements belong to the foreground or background or to the same object. We used three distinct stimuli that engage visual scene segmentation mechanisms based on motion. They involved perceptual grouping, transparent motion, and depth perception. Brain activity associated with all three mechanisms converged in the same parietal region with concurrent deactivation of early visual areas. The results suggest that posterior parietal cortex is a hub involved in structuring visual scenes based on different motion cues, and that feedback modulates early cortical processing in accord with predictive coding theory.

Angiotensin II Triggers Peripheral Macrophage-to-Sensory Neuron Redox Crosstalk to Elicit Pain

Injury, inflammation, and nerve damage initiate a wide variety of cellular and molecular processes that culminate in hyperexcitation of sensory nerves, which underlies chronic inflammatory and neuropathic pain. Using behavioral readouts of pain hypersensitivity induced by angiotensin II (Ang II) injection into mouse hindpaws, our study shows that activation of the type 2 Ang II receptor (AT2R) and the cell-damage-sensing ion channel TRPA1 are required for peripheral mechanical pain sensitization induced by Ang II in male and female mice. However, we show that AT2R is not expressed in mouse and human dorsal root ganglia (DRG) sensory neurons. Instead, expression/activation of AT2R on peripheral/skin macrophages (Ms) constitutes a critical trigger of mouse and human DRG sensory neuron excitation. Ang II-induced peripheral mechanical pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral Ms. Furthermore, AT2R activation in Ms triggers production of reactive oxygen/nitrogen species, which trans-activate TRPA1 on mouse and human DRG sensory neurons via cysteine modification of the channel. Our study thus identifies a translatable immune cell-to-sensory neuron signaling crosstalk underlying peripheral nociceptor sensitization. This form of cell-to-cell signaling represents a critical peripheral mechanism for chronic pain and thus identifies multiple druggable analgesic targets.

SIGNIFICANCE STATEMENT Pain is a widespread health problem that is undermanaged by currently available analgesics. Findings from a recent clinical trial on a type II angiotensin II receptor (AT2R) antagonist showed effective analgesia for neuropathic pain. AT2R antagonists have been shown to reduce neuropathy-, inflammation- and bone cancer-associated pain in rodents. We report that activation of AT2R in macrophages (Ms) that infiltrate the site of injury, but not in sensory neurons, triggers an intercellular redox communication with sensory neurons via activation of the cell damage/pain-sensing ion channel TRPA1. This M-to-sensory neuron crosstalk results in peripheral pain sensitization. Our findings provide an evidence-based mechanism underlying the analgesic action of AT2R antagonists, which could accelerate the development of efficacious non-opioid analgesic drugs for multiple pain conditions.

This Week in The Journal

Regional Distribution of CNS Antigens Differentially Determines T-Cell Mediated Neuroinflammation in a CX3CR1-Dependent Manner

T cells continuously sample CNS-derived antigens in the periphery, yet it is unknown how they sample and respond to CNS antigens derived from distinct brain areas. We expressed ovalbumin (OVA) neoepitopes in regionally distinct CNS areas (Cnp-OVA and Nes-OVA mice) to test peripheral antigen sampling by OVA-specific T cells under homeostatic and neuroinflammatory conditions. We show that antigen sampling in the periphery is independent of regional origin of CNS antigens in both male and female mice. However, experimental autoimmune encephalomyelitis (EAE) is differentially influenced in Cnp-OVA and Nes-OVA female mice. Although there is the same frequency of CD45^high CD11b+ CD11c+ CX3CL1+ myeloid cell–T-cell clusters in neoepitope-expressing areas, EAE is inhibited in Nes-OVA female mice and accelerated in CNP-OVA female mice. Accumulation of OVA-specific T cells and their immunomodulatory effects on EAE are CX3C chemokine receptor 1 (CX3CR1) dependent. These data show that despite similar levels of peripheral antigen sampling, CNS antigen-specific T cells differentially influence neuroinflammatory disease depending on the location of cognate antigens and the presence of CX3CL1/CX3CR1 signaling.

SIGNIFICANCE STATEMENT Our data show that peripheral T cells similarly recognize neoepitopes independent of their origin within the CNS under homeostatic conditions. Contrastingly, during ongoing autoimmune neuroinflammation, neoepitope-specific T cells differentially influence clinical score and pathology based on the CNS regional location of the neoepitopes in a CX3CR1-dependent manner. Altogether, we propose a novel mechanism for how T cells respond to regionally distinct CNS derived antigens and contribute to CNS autoimmune pathology.

Selective Role of RGS9-2 in Regulating Retrograde Synaptic Signaling of Indirect Pathway Medium Spiny Neurons in Dorsal Striatum

In the striatum, medium spiny neurons (MSNs) are heavily involved in controlling movement and reward. MSNs form two distinct populations expressing either dopamine receptor 1 (D1-MSN) or dopamine receptor 2 (D2-MSN), which differ in their projection targets and neurochemical composition. The activity of both types of MSNs is shaped by multiple neuromodulatory inputs processed by GPCRs that fundamentally impact their synaptic properties biasing behavioral outcomes. How these GPCR signaling cascades are regulated and what downstream targets they recruit in D1-MSN and D2-MSN populations are incompletely understood. In this study, we examined the cellular and molecular mechanisms underlying the action of RGS9–2, a key GPCR regulator in MSNs implicated in both movement control and actions of addictive drugs. Imaging cultured striatal neurons, we found that ablation of RGS9–2 significantly reduced calcium influx through NMDARs. Electrophysiological recordings in slices confirmed inhibition of NMDAR function in MSNs, resulting in enhanced AMPAR/NMDAR ratio. Accordingly, male mice lacking RGS9–2 displayed behavioral hypersensitivity to NMDAR blockade by MK-801 or ketamine. Recordings from genetically identified populations of striatal neurons revealed that these changes were selective to D2-MSNs. Surprisingly, we found that these postsynaptic effects resulted in remodeling of presynaptic inputs to D2-MSNs increasing the frequency of mEPSC and inhibiting paired-pulse ratio. Pharmacological dissection revealed that these adaptations were mediated by the NMDAR-dependent inhibition of retrograde endocannabinoid signaling from D2-MSNs to CB1 receptor on presynaptic terminals. Together, these data demonstrate a novel mechanism for pathway selective regulation of synaptic plasticity in MSNs controlled by GPCR signaling.

SIGNIFICANCE STATEMENT This study identifies a role for a major G-protein regulator in controlling synaptic properties of striatal neurons in a pathway selective fashion.

The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans Neuromuscular Junction

Communications across chemical synapses are primarily mediated by neurotransmitters and their postsynaptic receptors. There are diverse molecular systems to localize and regulate the receptors at the synapse. Here, we identify HPO-30, a member of the claudin superfamily of membrane proteins, as a positive regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes at the NMJ and shows genetic and physical association with the LAChR subunits LEV-8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the hermaphrodite C. elegans, we demonstrate that HPO-30 functions through Neuroligin at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this work suggests a novel function for a tight junction protein in maintaining normal receptor levels at the NMJ.

SIGNIFICANCE STATEMENT Claudins are a large superfamily of membrane proteins. Their role in maintaining the functional integrity of tight junctions has been widely explored. Our experiments suggest a critical role for the claudin-like protein, HPO-30, in maintaining synaptic levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the acetylcholine-mediated conductance in adult Caenorhabditis elegans; however, they play a significant functional role in worm locomotion. This study provides a new perspective in the study of LAChR physiology.

Neural Computations Underlying Causal Structure Learning

Behavioral evidence suggests that beliefs about causal structure constrain associative learning, determining which stimuli can enter into association, as well as the functional form of that association. Bayesian learning theory provides one mechanism by which structural beliefs can be acquired from experience, but the neural basis of this mechanism is poorly understood. We studied this question with a combination of behavioral, computational, and neuroimaging techniques. Male and female human subjects learned to predict an outcome based on cue and context stimuli while being scanned using fMRI. Using a model-based analysis of the fMRI data, we show that structure learning signals are encoded in posterior parietal cortex, lateral prefrontal cortex, and the frontal pole. These structure learning signals are distinct from associative learning signals. Moreover, representational similarity analysis and information mapping revealed that the multivariate patterns of activity in posterior parietal cortex and anterior insula encode the full posterior distribution over causal structures. Variability in the encoding of the posterior across subjects predicted variability in their subsequent behavioral performance. These results provide evidence for a neural architecture in which structure learning guides the formation of associations.

SIGNIFICANCE STATEMENT Animals are able to infer the hidden structure behind causal relations between stimuli in the environment, allowing them to generalize this knowledge to stimuli they have never experienced before. A recently published computational model based on this idea provided a parsimonious account of a wide range of phenomena reported in the animal learning literature, suggesting a dedicated neural mechanism for learning this hidden structure. Here, we validate this model by measuring brain activity during a task that involves both structure learning and associative learning. We show that a distinct network of regions supports structure learning and that the neural signal corresponding to beliefs about structure predicts future behavioral performance.

Targeting TrkB with a Brain-Derived Neurotrophic Factor Mimetic Promotes Myelin Repair in the Brain

Methods to promote myelin regeneration in response to central myelin loss are essential to prevent the progression of clinical disability in demyelinating diseases. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to promote myelination during development via oligodendrocyte expressed TrkB receptors. Here, we use a structural mimetic of BDNF to promote myelin regeneration in a preclinical mouse model of central demyelination. In female mice, we show that selective targeting of TrkB with the BDNF-mimetic enhances remyelination, increasing oligodendrocyte differentiation, the frequency of myelinated axons, and myelin sheath thickness after a demyelinating insult. Treatment with exogenous BDNF exerted an attenuated effect, increasing myelin sheath thickness only. Further, following conditional deletion of TrkB from premyelinating oligodendrocytes, we show the effects of the BDNF-mimetic on oligodendrocyte differentiation and remyelination are lost, indicating these are dependent on oligodendrocyte expression of TrkB. Overall, these studies demonstrate that targeting oligodendrocyte TrkB promotes in vivo remyelination in the brain.

SIGNIFICANCE STATEMENT Novel strategies to promote myelin regeneration are required to prevent progressive neurodegeneration and clinical disability in patients with central demyelinating disease. Here, we test whether selectively targeting the TrkB receptor on the myelin-producing oligodendrocytes, can promote remyelination in the brain. Using a structural mimetic of its native ligand, BDNF, we show that stimulation of TrkB enhances remyelination, increasing oligodendrocyte differentiation, the frequency of myelinated axons and thickness of the myelin sheath following a demyelinating insult. Further, we show that these effects are dependent on the phosphorylation of oligodendrocyte expressed TrkB receptors in vivo. Overall, we demonstrate that selective targeting of TrkB has therapeutic potential to promote remyelination in the brain.

Beta-Blocker Propranolol Modulates Decision Urgency During Sequential Information Gathering

Arbitrating between timely choice and extended information gathering is critical for effective decision making. Aberrant information gathering behavior is thought to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder, but we know little about the underlying neurocognitive control mechanisms. In a double-blind, placebo-controlled drug study involving 60 healthy human subjects (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering during performance of an information sampling task. We show that modulating noradrenaline function with 40 mg of the β-blocker propranolol leads to decreased information gathering behavior. Modulating dopamine function via a single dose of 400 mg of amisulpride revealed some effects that were intermediate between those of propranolol and placebo. Using a Bayesian computational model, we show that sampling behavior is best explained by inclusion of a nonlinear urgency signal that promotes commitment to an early decision. Noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.

SIGNIFICANCE STATEMENT Knowing when to stop gathering information and commit to a choice option is nontrivial. This is an important element in arbitrating between information gain and energy conservation. In this double-blind, placebo-controlled drug study, we investigated the role of catecholamines noradrenaline and dopamine on sequential information gathering. We found that blockade of noradrenaline led to a decrease in information gathering. Dopamine blockade showed an intermediate, but nonsignificant, effect. Using a Bayesian computational model, we show that this noradrenaline effect is driven by increased decision urgency, a signal that reflects an escalating subjective cost of sampling. The observation that noradrenaline modulates decision urgency suggests new avenues for treating patients that show information gathering deficits.

Drug Refraining and Seeking Potentiate Synapses on Distinct Populations of Accumbens Medium Spiny Neurons

Cocaine-associated cues and contexts can precipitate drug seeking in humans and in experimental animals. Glutamatergic synapses in the core subcompartment of the nucleus accumbens (NAcore) undergo transient potentiation in response to presenting drug-associated cues. The NAcore contains two populations of medium spiny neurons (MSNs) that differentially express D1 or D2 dopamine receptors. By recording the ratio of AMPA and NMDA glutamate receptor currents (AMPA/NMDA ratio) from MSNs in NAcore tissue slices, we endeavored to understand which subpopulation of MSNs was undergoing transient potentiation. Transgenic female and male mice differentially expressing fluorescent reporters in D1 or D2 MSNs were withdrawn for 2–3 weeks after being trained to self-administer cocaine. In some mice, discrete cocaine-conditioned cues were isolated from the drug-associated context via extinction training, which causes rodents to refrain from drug seeking in the extinguished context. By measuring AMPA/NMDA ratios in the drug context with or without contextual or discrete cues, and with or without extinction training, we made the following three discoveries: (1) mice refraining from cocaine seeking in the extinguished context showed selective elevation in AMPA/NMDA ratios in D2 MSNs; (2) without extinction training, the drug-associated context selectively increased AMPA/NMDA ratios in D1 MSNs; (3) mice undergoing cue-induced cocaine seeking after extinction training in the drug-associated context showed AMPA/NMDA ratio increases in both D1 and D2 MSNs. These findings reveal that the NAcore codes drug seeking through transient potentiation of D1 MSNs, and that refraining from cocaine seeking in an extinguished context is coded through transient potentiation of D2 MSNs.

SIGNIFICANCE STATEMENT Relapse is a primary symptom of addiction that can involve competition between the desire to use drugs and the desire to refrain from using drugs. Drug-associated cues induce relapse, which is correlated with transiently potentiated glutamatergic synapses in the nucleus accumbens core. We determined which of two cell populations in the accumbens core, D1-expressing or D2-expressing neurons, undergo transient synaptic potentiation. After being trained to self-administer cocaine, mice underwent withdrawal, some with and others without extinguishing responding in the drug-associated context. Extinguished mice showed transient potentiation in D2-expressing neurons in the extinguished environment, and all mice engaged in context-induced or cue-induced drug seeking showed transient potentiation of D1-expressing neurons. A simple binary engram in accumbens for seeking drugs and refraining from drugs offers opportunities for cell-specific therapies.

Correction: Sung et al., "Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTR in Nociception"

Interpreting competitive adsorption of arsenate and phosphate on nanosized iron (hydr)oxides: effects of pH and surface loading

Abstract

Arsenate and phosphate have similar properties due to their electrochemical structures, but their environmental impacts are unique. The abundance and competition of arsenate and phosphate determine their bioavailability and leachability; thus, it is essential to understand their fate in the soil environment. In this study, the effects of pH and surface loading on the competitive adsorption of arsenate and phosphate on four iron (hydr)oxides were evaluated by employing the Langmuir isotherm, competitive sorption ratio (CSR), and competition effect (CE). The stability and transformation of the iron (hydr)oxides were also assessed. Various adsorption patterns were observed in the single and mixed treatments by controlling the addition of oxyanions, pH, surface loading, and type of iron (hydr)oxides. Arsenate was preferentially adsorbed at a low pH, whereas phosphate showed the opposite trend. The CE_As(V),P(V) was close to zero at low surface density (no competition) and sequentially changed to negative or positive values with increasing surface density, indirectly indicating the sequential development of promotive and competitive effects. Transformation in goethite was identified at a high pH with the presence of oxyanions, except that no transformation was observed upon the addition of oxyanions and with pH change. However, the stability of the iron (hydr)oxides decreased at a low pH and with the presence of phosphate, arsenate, or both. The hematite showed a significant promotive effect regardless of the pH. Our study revealed that the pH, surface loading, and type of iron (hydr)oxides are intercorrelated and simultaneously affect the adsorption characteristics of oxyanions and the stability of iron (hydr)oxides.

Councilor's Meeting/General Assembly of Members at the International Investigative Dermatology 2018 (IID2018)

Are Risk Factors for Coronary Artery Disease Different in Persons With and Without Obesity?

Metabolic Syndrome and Related Disorders, Ahead of Print.

The Mastocytosis Society Survey on Mast Cell Disorders: Part 2-Patient Clinical Experiences and Beyond

Publication date: Available online 8 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Nancy Russell, Susan Jennings, Blair Jennings, Valerie Slee, Lisa Sterling, Mariana Castells, Peter Valent, Cem Akin

Abstract

Background

Mast cell diseases such as mastocytosis and mast cell activation syndrome involve abnormal proliferation and/or activation of these cells leading to many clinically relevant symptoms.

Objective

In order to determine the characteristics and experiences of people known or suspected to have a mast cell disorder, The Mastocytosis Society, a US based patient advocacy, research and education organization, conducted a survey of patients.

Methods

This web-based survey was publicized through specialty clinics and the Society's newsletter, Web site and online blogs. Both online and paper copies of the questionnaire were provided together with required statements of consent.

Results

The first set of results from this survey of 420 respondents has been previously published; the second set is presented in this article. These results include source(s) of diagnosis, clinical and laboratory tests reported, comorbidities, dietary practices, possible familial occurrence of mast cell diseases, and perceptions concerning mast cell related medical care needs in the United States.

Conclusions

These patient survey results are provided to assist medical professionals in learning patients' perceptions of their experiences and to give patients with mast cell disorders and caregivers the opportunity to compare experiences with those of other affected individuals.

A large single hospital experience using drug provocation testing and rapid drug desensitization in hypersensitivity to antineoplastic and biological agents

Publication date: Available online 8 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Ricardo Madrigal-Burgaleta, Lorena Bernal-Rubio, Maria Pilar Berges-Gimeno, Laura Victoria Carpio-Escalona, Patricia Gehlhaar, Emilio Alvarez-Cuesta

ABSTRACT

Background

Large-scale studies of Drug Provocation Testing (DPT) or Rapid Drug Desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions

Objective

Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience.

Methods

7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, ST, risk-assessment, specific-IgE, DPT) prior to RDD. Candidate patients underwent RDD using the RCUH-protocol. Cetuximab reactors underwent one-bag RDDs.

Results

1,027 intravenous RDDs were performed using the RCUH-protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1,026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough-reactions occurred in 88% of RDDs. Most breakthrough-reactions were mild. 341 DPTs were performed, and 229 were negative (67%). DPTs helped exclude hypersensitivity in 44% of referred-patients (229/515). Additionally, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients.

Conclusions

This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions and risk considerations which need a tailored approach (taking into account the three prominent drug categories: platins, taxanes and biologicals).

Equilibrium study of binary mixture biosorption of Cr(III) and Zn(II) by dealginated seaweed waste: investigation of adsorption mechanisms using X-ray photoelectron spectroscopy analysis

Abstract

The alginate extraction residue (RES) from the Brazilian Sargassum filipendula was successfully employed as biosorbent in this binary equilibrium study, revealing a greater affinity and selectivity for Cr(III) than for Zn(II). Experimental results also revealed that the process is of endothermic nature and well adjusted by Langmuir–Freundlich binary model. The X-ray photoelectron spectroscopy (XPS) analysis revealed that coordination with hydroxyl groups of RES prevailed in Cr removal, followed by carboxyl-metal complexation. As far as Zn(II) is concerned, ion exchange with carboxylate groups of RES was the largest contributor. Nevertheless, scanning electron microscopy coupled with Fourier transform infrared spectroscopy indicated the participation of sulfate functions in a minor degree.

Facile preparation of microscale hydrogel particles for high efficiency adsorption of bisphenol A from aqueous solution

Abstract

Hydrogel microparticles (HMPs) were synthesized via reverse emulsion/UV light polymerization and employed as adsorbents for removing bisphenol A (BPA) from aqueous solution. Results demonstrated the smooth surface of HMPs, with particle size ranging from 137 to 535 μm. Functional groups, including –OH, C–O, C=O, and C–H, are all involved in BPA adsorption confirmed by FTIR. Effect of solution pH, contact time, and initial BPA concentration on adsorption process was examined. The adsorption capacity was found pH independent below pH 8.0 and decreased when pH values greater than 8.0. The maximum adsorption capacity of the HMPs for BPA was 174.77 mg/g. The adsorption process achieved an equilibrium state within 30 min by the pseudo-second-order kinetic rather than the other kinetic models and was fitted well with the Freundlich linear isotherm model. Also, the obtained isotherms reflected the formation of S-type isotherm curve according to Giles's classification. The BPA loaded on the HMPs could be totally regenerated by methanol/dimethylsulfoxide and can be used for five cycles maintaining 100% of adsorption capacity. When the HMPs were applied for the treatment of spiked real surface water, excellent results were also achieved indicating the high efficiency and potential of the adsorbent.

Light induced DNA-functionalized TiO2 nanocrystalline interface: Theoretical and experimental insights towards DNA damage detection

Publication date: Available online 8 August 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Bayu Tri Murti, Athika Darumas Putri, Suvardhan Kanchi, Myalowenkosi I. Sabela, Krishna Bisetty, Ashutosh Tiwari, Inamuddin, Abdullah M. Asiri

Abstract

Owing to the emerging applications of DNA-functionalized TiO₂ nanocrystals towards DNA damage detection, it is inevitable to understand the better chemistry as well as in-depth molecular interaction phenomena. Fundamentally, energy difference underlies the layer-by-layer construction, resulted in the increase of the interaction energy and thus, altering the electrochemical behavior. Herein, Density functional theory (DFT) calculations were performed using DMol3 and DFTB+ codes successfully to elucidate the structural, electronics, and vibrational properties of the layer-by-layer components composing ss-DNA/dopamine/TiO₂/FTO. The obtained results are in good agreement with the experimental findings. The band gaps of FTO and TiO₂ were computationally obtained at 3.335 and 3.136 eV which are comparable with the experimental data (3.500 eV; FTO and 3.200 eV; TiO₂). Frontier orbital analysis is also considered to elucidate their electron transfer phenomena. Further, a 100 ns MD simulations are carried out using canonical ensemble embedded with COMPASS-Universal Forcefields generating useful thermodynamics parameters. Binding energies indicate increasing interaction energies for the layer-by-layer nanosystem, in agreement with the increasing diameter of electrochemical impedance spectroscopy (EIS) semicircle. Our results reveal the fundamental understanding of the DNA-functionalized TiO₂ nanocrystals down to molecular and electronic level and further, paving a way of its application towards nanoelectrochemical DNA biosensors.

Graphical abstract

Eliminating interference by anthocyanins when determining the porphyrin ratio of red plant leaves

Publication date: Available online 8 August 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Tzan-Chain Lee, Tin-Han Shih, Meng-Yuan Huang, Kuan-Hung Lin, Wen-Dar Huang, Chi-Ming Yang

Abstract

Anthocyanins (Ants) are water-soluble secondary metabolites that are responsible for red colour of plant leaves. To determine photosynthetic pigments, 80% acetone was used to extract Ants from Ant-containing leaves of test plants. However, using the 80% acetone extraction method can lead to interference between chlorophylls (Chls) and Ants. Porphyrins, such as protoporphyrin IX (PPIX), Mg-protoporphyrin IX (MgPP), and protochlorophyllide (Pchlide), are Chl biosynthetic intermediates and demonstrate photospectrometric characteristics similar to those of Chl. Although the ether/water extraction method was able to remove Ants interference when detecting porphyrins, the porphyrins extraction efficiency was lower than that of the 80% acetone extraction method. Low Ants levels interfered with individual porphyrin ratios, and the extent of the effect was correlated with Ants concentrations. We developed the three equations could eliminate interference by Ants when determining the porphyrin molecular percentage (%) and were comprehensively applied to all tested species of Ants-containing leaves.

Graphical abstract

Developments of nano-TiO2 incorporated hydroxyapatite/PEEK composite strut for cervical reconstruction and interbody fusion after corpectomy with anterior plate fixation

Publication date: Available online 8 August 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Fanlei Kong, Zhihong Nie, Zhongpo Liu, Shibin Hou, Jiangfeng Ji

Abstract

The technique of anterior cervical corpectomy and fusion (ACCF) for strut grafting has become a widespread and actively applied for many cervical complaints including cervical degeneration of the intervertebral disks, cervical trauma, cancer, rheumatoid arthritis and multilevel cervical spondylotic diseases. To avoid the complications of the old techniques, the construct stability and long anterior screw-plate designs of the bone strut have been improved by using effective biomaterials. The nanostructured hydroxyapatite (HAp) incorporated with biocompatible polymer matrixes is an effective biomedical material and creating a functional properties applied for different tissue replacements such as dental, hips, knees, tendon and ligaments and tissue repair for maxillofacial reconstruction, stabilization of the jaw bone and spinal fusion. In the present investigation, we have successfully designed cylindrical nano titanium dioxide (n-TiO₂) interbody fusion with anterior plate fixation. The n-TiO₂ incorporated HAp/ Polyetheretherketone (PEEK) nanocomposite strut has a superior mechanical properties and larger contact area with high fusion rates as compared with the HAp/PEEK strut in the absence of n-TiO₂ nanoparticles. It is highly able to provide appropriate strength and biological activity similar to the conventional titanium cage and also mainly it has been minimizes subsidence value. The synthesized novel material of n-TiO2 incorporated HAp/PEEK nanocomposite strut is scientifically given effective outcomes for fusion and reconstruction of the ACCF.

Graphical Abstract

Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in Patients With Diabetes

This case-control study evaluates the association between use of dipeptidyl-peptidase 4 (DPP-4) inhibitors and development of bullous pemphigoid (BP) in patients with diabetes and characterizes those patients who develop DPP-4 inhibitor–associated BP.

Topical Crisaborole—A Potential Treatment for Recalcitrant Palmoplantar Psoriasis

This case report describes the use of topical crisaborole to treat previously treatment-refractory palmoplantar psoriasis

Evaluation of a Brief Dermatologist-Delivered Intervention vs Usual Care on Sun Protection Behavior

This longitudinal controlled cohort study examines the association of a brief dermatologist-delivered intervention with patient satisfaction and sun protection behavior among adults receiving dermatology care.

Avoiding and Managing Medicare Fraud and Abuse Investigations of Mohs Surgery

This Viewpoint discusses ways dermatologists can manage and avoid investigations by the US Department of Justice and the Centers for Medicare & Medicaid Services for alleged Medicare fraud and abuse related to Mohs surgery.

A White Patch on the Tongue

An 80-year-old woman presented with an asymptomatic white patch affecting the tongue of 1 month's duration; she had a 15-year history of oral lichen planus managed with treatment. What is your diagnosis?

A Twitter Analysis of the #DontFryDay Campaign

This study assessed the reach of the "Don't Fry Day" campaign on Twitter, using the hashtag #DontFryDay, and identified what types of individuals and/or tweeters are engaging in the campaign.

Assessing the Competence of Aging Physicians Who Are Young at Heart

This Viewpoint discusses the issues involved in assessing the professional competence of aging physicians as increasing numbers of physicians continue to work past the age of 65 years.

Distinguishing Mild, Moderate, and Severe Hidradenitis Suppurativa—Reply

In Reply We are grateful for the very constructive and positive feedback from Kokolakis and Sabat regarding our newly proposed Severity Assessment of Hidradenitis Suppurativa (SAHS) score.

Dynamic Trichoscopy

This Viewpoint discusses how the dermoscope is a practical instrument for use in routine practice and describes how its shortcomings can be overcome with increasing familiarity with the use of dynamic vs static trichoscopy.

Dupilumab Treatment of Very Severe Refractory Atopic Hand Eczema

This case report describes the use of dupilumab to treat a patient with very severe refractory atopic hand eczema.

Lentigo Maligna—Challenges, Observations, Imiquimod, Confocal Microscopy, and Personalized Treatment

The word melanoma imparts considerable fear and concern in patients. Fortunately, for patients with the lentigo maligna (LM) subtype of melanoma in situ, there is overall good prognosis. The challenge of LM, however, is that it has the highest rate of local recurrence (approximately 20%) of all melanoma subtypes when treated by standard surgical excision alone, owing to frequent, unpredictable, subclinical extension. To reduce this risk, the use of Mohs surgery or staged excision has consistently demonstrated lower recurrence rates of 0.3% to 2.2% yet requires larger surgical margins for histological clearance than other in situ melanoma subtypes. Moyer et al also demonstrated that with increasing lesion size, both the surgical margin required to clear the lesion and the risk of local recurrence increased, suggesting increased subclinical spread with increasing lesion size. In addition, LM is typically located in the head and neck area, a complex zone with potential cosmetic and functional impairment owing to extensive surgery. Finally, differentiating LM from background atypical melanocytic hyperplasia can be challenging. Thus, treatments directed toward reducing the extent of surgery, minimizing morbidity, and providing a cure would enhance patient outcomes.

Friedrich Daniel von Recklinghausen

Friedrich Daniel von Recklinghausen, MD, was one of the most prominent German pathologists of his time. His contributions resulted in the identification of several eponymous conditions, most notably von Recklinghausen disease, or neurofibromatosis type 1.

Lentigo Maligna Treated With Off-label Neoadjuvant Imiquimod

This medical record review examines the rate of recurrence of lentigo maligna in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions.

Cutavirus Infection in Primary Cutaneous B- and T-Cell Lymphoma

This virological study examines the association of cutavirus DNA with different types of cutaneous B-cell lymphoma and cutaneous T-cell lymphoma in lesional skin samples.

Assessment of a Predictive Scoring Model for Dermoscopy of Subungual Melanoma In Situ

This cohort study identifies the dermoscopic features of subungual melanoma in situ in a Korean population and assesses a predictive scoring model that distinguishes the diagnosis of subungual melanoma in situ from longitudinal melanonychia in patients with pigmented nails.

Strengthening the Case for the Role of Thrombophilia in Calciphylaxis

In Reply We thank Hickson and colleagues for their interest in our Original Investigation titled "Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease: A Case-Control Study" on the role of hypercoagulable conditions in the development of calciphylaxis in patients with renal disease.

Decision Tree Model vs Traditional Measures for Associations of Sun-Protective Behaviors

This cross-sectional national survey assesses whether decision-based modeling can identify patterns of sun-protective behaviors and sun sensitivity associated with the likelihood of sunburn among US adults.

Underuse of the Sentinel Lymph Node Biopsy for High-Risk SCC of the Skin—Reply

In Reply We read with interest the response by Glazer et al regarding our study on the underuse of sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma (cSCC) and noted several important inquiries and comments.

Association of Inadequately Controlled Disease With Patient-Reported Disease Burden in Atopic Dermatitis

This cross-sectional study examines the association of atopic dermatitis severity and disease control with the patient-reported disease burden in clinical practice.

August 2018 Issue Highlights

Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib

This phase 2 randomized clinical trial investigates if topical targeting of topical tropomyosin receptor kinase (TRK) with an inhibitor, pegcantratinib, is safe and efficacious in treating tumors in patients with CYLD cutaneous syndrome.

Skin Cancer Detection In Vivo With Reflectance Confocal Microscopy Performed by a Novice Reader

This study evaluates the learning curve, diagnostic accuracy, and challenges for a novice reader of reflectance confocal microscopy for determining a diagnosis of skin cancer.

Clinical and Laboratory Markers of Relapse in Cutaneous Polyarteritis Nodosa

This case series identifies clinical and laboratory markers that may be associated with relapse among patients with cutaneous polyarteritis nodosa.

Trichophyton erinacei Transmitted to a Pregnant Woman From Her Pet Hedgehogs

This case report describes a pregnant woman who developed tinea manus from Trichophyton erinacei infection transmitted to her from her pet hedgehogs.

Human Papillomavirus Vaccine to Treat Cutaneous Basaloid Squamous Cell Carcinomas

This case report describes a woman with multiple, inoperable cutaneous basaloid squamous cell carcinomas who was treated with 9-valent human papillomavirus vaccine.

Recent advances in development of cell-free protein synthesis systems for fast and efficient production of recombinant proteins

Abstract

Cell-free protein synthesis has emerged in recent years as a powerful tool that can potentially transform the production of recombinant proteins. Cell-free protein synthesis harnesses the synthetic power of living cells while eliminating many of the constraints of traditional cell-based gene expression methods. Due to the lack of physical barriers separating the protein synthesis machinery from the surrounding environment, a cell-free protein synthesis reaction mixture can be directly programmed using diverse genetic material for the instant production of recombinant proteins without complicated cloning procedures. However, a number of issues must be addressed for this technology to be widely accepted as an alternative platform for protein production, including quality-control of translation machinery preparations, and high reagent cost. This review describes recent efforts to make cell-free protein synthesis more affordable and more easily accessible for generic applications.

Role of tyrosine residue (Y213) in nuclear retention of PCNA1 in human malaria parasite Plasmodium falciparum

Abstract

Proliferating Cell Nuclear Antigen (PCNA) undergoes several post-translational modifications including phosphorylation leading to its regulation in mammalian and yeast systems. Plasmodium falciparum possesses two PCNAs (PCNA1 & PCNA2) with an edge of PfPCNA1 over PfPCNA2 for DNA replication. Recent phospho-proteome data report phosphorylation of S191 residue without its functional implication. In mammalian cells, phosphorylation of HsPCNA at Y211 stabilizes chromatin bound PCNA. We find tyrosine (but not S191) to be conserved in PfPCNAs and it is important for its nuclear localization and foci formation of PfPCNA1. Further, a Y213F mutation in PfPCNA1 leads to its functional loss both in yeast and parasite. We highlight the importance of evolutionarily conserved tyrosine in PCNA from parasite to mammal linked with DNA replication and cell proliferation.

Controversy on the Use of Povidone-Iodine in Chronic Wounds

Skin Pharmacol Physiol 2018;31:261

Translational Insights into Gastrointestinal Stromal Tumor and Current Clinical Advances

Abstract

Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma of the gastrointestinal tract and, in the vast majority of cases, is characterized by activating mutations in KIT or, less commonly, PDGFRA. Mutations in these type III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the majority of KIT primary mutations respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib. However, drug resistance develops over time, most commonly due to secondary kinase mutations. Sunitinib and regorafenib are approved for the treatment of imatinib-resistant GIST in the second and third lines, respectively. However, resistance to these agents also develops and new therapeutic options are needed. In addition, a small number of GISTs harbor primary activating mutations that are resistant to currently available TKIs, highlighting an additional unmet medical need. Several novel and selective TKIs that overcome known mechanisms of resistance in GIST have been developed and show promise in early clinical trials. Additional emerging targeted therapies in GIST include modulation of cellular signaling pathways downstream of KIT, antibodies targeting KIT and PDGFRA and immune checkpoint inhibitors. These advancements highlight the rapid evolution in the understanding of this malignancy and provide perspective on the encouraging horizon of current and forthcoming therapeutic strategies for GIST.

Prognostic utility of HPV specific testing in addition to p16 immunohistochemistry in oropharyngeal squamous cell carcinoma

First evaluation of floating microplastics in the Northwestern Adriatic Sea

Abstract

Plastic pollution in the marine environment is becoming a problem of global concern, and the Mediterranean is believed to be one of the worst affected regional seas. The present study presents data on floating microplastics in the Northwestern Adriatic Sea in order to evaluate the possible contribution of two significant potential sources: the lagoon of Venice and the Po River. Samples were collected in March and April 2014 along two transects located off Pellestrina Island (Venice) and the Po Delta, each consisting of four sampling stations at 0.5, 3, 10, and 20 km from the shoreline. Microplastics were quantified and classified according to their colors and shapes and analyzed by micro-attenuated total reflection-FT-IR. Microplastics were found in all samples, albeit with high spatial and temporal variability. The highest concentrations were observed in March at the offshore station of the Pellestrina transect (10.4 particles m⁻²) and the two landward stations off the Po Delta (2.1 and 4.3 particles m⁻²), highlighting the influence of various factors, such as surface circulation and river discharges, in determining specific accumulation patterns. The most common polymers were polyethylene and polypropylene, and most of the particles were secondary microplastics (83.5%). The patchy distribution of microplastics observed in the study area is driven by hydrodynamic and meteorological factors acting on short time scales.

Characterization and adsorption capacity of potassium permanganate used to modify activated carbon filter media for indoor formaldehyde removal

Abstract

This study examined the effect of potassium permanganate (KMnO₄)-modified activated carbon for formaldehyde removal under different face velocities and different initial formaldehyde concentrations in building environment. We chose the coconut shell activated carbon due to their high density and purity. Moreover, they have a clear environmental advantage over coal-based carbons, particularly in terms of acidification potential. The chemical properties were characterized by FTIR to show the functional groups, EDS to calculate each component of their energy bands to know how the ratio is. Also, the morphology of the surface was examined with scanning electron microscopy (SEM). The BET determines specific surface area, pore size, and pore volume. It was found that where the initial formaldehyde concentration and the face velocity are low, adsorption capacity is high. The adsorption isotherms of formaldehyde on modified activated carbon are well fitted by both Langmuir and Freundlich equations. The rate parameter for the pseudo-first-order model, pseudo-second-order model, and intraparticle diffusion model was compared. The correlation coefficient of pseudo-second-order kinetic model (0.999 > R² > 0.9548) is higher than the coefficient of pseudo-first-order kinetic model (0.5785 < R² < 0.8755) and intraparticle diffusion model (0.9752 < R² < 0.9898). Thus, pseudo-second-order kinetic model is more apposite to discuss the adsorption kinetic in this test, and the overall rate of the modified activated carbon adsorption process appears to be influenced by more than one step that is both the intraparticle diffusion model and membrane diffusion.

Three‐step algorithm for biological therapy targeted IgE and IL‐5 in severe asthma

Immunity, Inflammation and Disease, EarlyView.

Histiocytofibrome avec induction sébacée

Publication date: Available online 7 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): E. Lorier Roy, M.-H. Jégou, A. Osio

Résumé

Introduction

L'histiocytofibrome, ou dermatofibrome (DF), est une lésion bénigne commune revêtant de multiples aspects cliniques et histologiques. Le phénomène d'induction sébacée en regard d'un dermatofibrome est rare et peu décrit. L'observation détaillée d'un cas de DF avec induction sébacée permet de préciser et d'illustrer ici la sémiologie clinique et dermatoscopique de cette lésion, ainsi que celle de ses diagnostics différentiels.

Observation

Un homme de 52 ans consultait pour un examen de surveillance, qui révélait une lésion papuleuse ferme du milieu du dos. La surface de la lésion apparaissait comme une zone un peu pigmentée dans sa partie supérieure, faite de plusieurs petits lobules blanchâtres. L'examen histologique concluait à un histiocytofibrome avec induction sébacée.

Discussion

Le phénomène d'induction sébacée en regard d'un dermatofibrome est peu fréquent ; dans la très grande majorité des cas, il est observé sur la région des épaules. L'aspect dermatoscopique de surface, avec de multiples globules ou structures compactes arrondies blanchâtres (clods) regroupés en amas, est caractéristique. L'origine du phénomène d'induction sébacée est inconnue ; on peut évoquer un micro-environnement favorable de la peau des épaules, associé à des facteurs de croissance sécrétés par le DF.

Summary

Background

Histiocytoma or dermatofibroma (DF) is a common benign skin tumour with several clinical and histopathological variants. Sebaceous induction overlying a dermatofibroma is rare and infrequently reported. Using a detailed clinical case, herein the semiological and dermoscopic features of this lesion are described and illustrated, and the differential diagnoses presented.

Patients and methods

A 52-year-old man consulted for a physical examination, which revealed a firm papular lesion of the upper middle back. The upper part of the nodule was covered by a slightly hyperpigmented surface, with numerous small whitish lobules. Microscopic examination revealed a dermatofibroma with sebaceous induction.

Discussion

Sebaceous induction overlying a dermatofibroma is not frequent, and it occurs in most cases on or near the shoulder. The typical dermoscopic pattern involves many whitish globules or clumps grouped into clusters. The aetiology is unknown but could stem from a conducive microenvironment in shoulder skin, associated with growth factors secreted by the DF.

Pemphigoïde bulleuse localisée sur lambeau cutané

Publication date: Available online 7 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): C. Ivan, H. Kassem Youssef, E. Backobi, F. Chouta Ngaha, H. Nojavan, C. Michel