Vulvite granulomateuse de type Miescher

Publication date: Available online 6 June 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): K. Alhazmi, S. Berville, M. Moyal-Barracco, F. Plantier
IntroductionLa chéilite de Miescher, isolée ou dans le cadre d'un syndrome de Melkerssohn-Rosenthal, est une inflammation granulomateuse rare de cause inconnue dont il existe un équivalent génital encore plus rare. Nous en décrivons un cas, avec son évolution sur douze années.ObservationUne femme de 27 ans présentait des poussées d'œdème vulvaire unilatéral, régressives au début puis aboutissant au fil du temps à des tuméfactions permanentes, vulvaire et périnéale. Les prélèvements histologiques montraient des granulomes histiocytaires épithélioïdes, si discrets qu'ils étaient passés inaperçus au début de l'évolution. L'œdème demeurait un signe isolé pendant douze ans et deux bilans digestifs à la recherche d'une maladie de Crohn étaient négatifs, permettant d'écarter ce diagnostic.DiscussionLa vulvite granulomateuse de type Miescher est un diagnostic d'élimination, essentiellement de la maladie de Crohn. Notre observation illustre la difficulté du diagnostic de cette pathologie rare et les incertitudes concernant sa physiopathologie. Le diagnostic impose de savoir répéter les prélèvements et pratiquer des biopsies profondes avec des niveaux de coupes répétés pour identifier les granulomes paravasculaires caractéristiques, parfois très discrets.BackgroundMiescher's cheilitis, whether occurring alone or as part of Melkersson-Rosenthal syndrome, is a rare type of granulomatous inflammation of unknown cause with an even rarer genital equivalent. Herein, we describe a case of the latter condition developing over a 12-year period.Patients and methodsA 27-year-old woman presented episodes of unilateral vulvar oedema, which initially regressed but resulted over time in permanent vulvar and perineal tumefaction. Histology revealed epithelioid histocytic granulomas so mild that they were not noticed at the start of the disease. The oedema remained the sole sign for 12years and two gastrointestinal screening tests for Crohn's disease proved negative, diagnosis of the latter condition was ruled out.DiscussionMiescher's granulomatous vulvitis requires differential diagnosis, essentially with regard to Crohn's disease. Our case illustrates the difficulty in diagnosing this rare disease as well as the uncertainties surrounding its physiopathology. Diagnosis rests upon repeated sampling and biopsies with repeated levels of sections in order to identify the characteristic perivascular granulomas, which may be very mild.

Exposure to Wood Dust, Microbial Components, and Terpenes in the Norwegian Sawmill Industry

Abstract

Sawmill workers are exposed to wood dust (a well-known carcinogen), microorganisms, endotoxins, resin acids (diterpenes), and vapours containing terpenes, which may cause skin irritation, allergy, and respiratory symptoms including asthma. The health effects of most of these exposures are poorly understood as most studies measure only wood dust. The present study assessed these exposures in the Norwegian sawmill industry, which processes predominantly spruce and pine. Personal exposures of wood dust, resin acids, endotoxin, fungal spores and fragments, mono-, and sesquiterpenes were measured in 10 departments in 11 saw and planer mills. The geometric mean (GM) and geometric standard deviation (GSD) thoracic exposures were: 0.09 mg m⁻³ dust (GSD 2.6), 3.0 endotoxin units (EU) m⁻³ (GSD 4.9), 0.4 × 10⁵ fungal spores m⁻³ (GSD 4.2), 2 × 10⁵ fungal fragments m⁻³ (GSD 3.2), and 1560 ng m⁻³ of resin acids (GSD 5.5). The GM (GSD) inhalable exposures were: 0.72 mg m⁻³ dust (2.6), 17 EU m⁻³ (4.3), 0.4 × 10⁵ fungal spores m⁻³ (3.8), and 7508 ng m⁻³ (4.4) of resin acids. The overall correlation between the thoracic and inhalable exposure was strong for resin acid (r_p = 0.84), but moderate for all other components (r_p = 0.34–0.64). The GM (GSD) exposure to monoterpenes and sesquiterpenes were 1105 µg m⁻³ (7.8) and 40 µg m⁻³ (3.9), respectively. Although mean exposures were relatively low, the variance was large, with exposures regularly exceeding the recommended occupational exposure limits. The exposures to spores and endotoxins were relatively high in the dry timber departments, but exposures to microbial components and mono-and sesquiterpenes were generally highest in areas where green (undried) timber was handled. Dust and resin acid exposure were highest in the dry areas of the sawmills. Low to moderate correlation between components (r_p ranging from 0.02 to 0.65) suggests that investigations of exposure–response associations for these components (both individually and combined) are feasible in future epidemiological studies.

Performance Comparison of Field Portable Instruments to the Scanning Mobility Particle Sizer Using Monodispersed and Polydispersed Sodium Chloride Aerosols

Abstract

This study compared the performance of the following field portable aerosol instrument sets to performance of the reference Scanning Mobility Particle Sizer (SMPS): the handheld CPC-3007, the portable aerosol mobility spectrometer (PAMS), the NanoScan scanning mobility particle sizer (NanoScan SMPS) combined with an optical particle sizer (OPS). Tests were conducted with monodispersed and polydispersed aerosols. Monodispersed aerosols were controlled at the approximate concentration of 1 × 10⁵ particles cm⁻³ and four monodispersed particle sizes of 30, 60, 100, and 300 nm were selected and classified for the monodispersed aerosol test, while three different steady-state concentration levels (low, medium, and high: ~8 × 10³, 5 × 10⁴, and 1 × 10⁵ particles cm⁻³, respectively) were selected for the polydispersed aerosol test. For all four monodispersed aerosol sizes, particle concentrations measured with the NanoScan SMPS were within 13% of those measured with the reference SMPS. Particle concentrations measured with the PAMS were within 25% of those measured with the reference SMPS. Concentrations measured with the handheld condensation particle counter were within 30% of those measured with the reference SMPS. For the polydispersed aerosols, the particle sizes and concentrations measured with the NanoScan-OPS compared most favorably with those measured with the reference SMPS for three different concentration levels of low, medium, and high (concentration deviations ≤10% for all three concentration levels; deviations of particle size ≤4%). Although the particle-size comparability between the PAMS and the reference SMPS was quite reasonable with the deviations within 10%, the polydispersed particle concentrations measured with the PAMS were within 36% of those measured with the reference SMPS. The results of this evaluation will be useful for selecting a suitable portable device for our next workplace study phase of respiratory protection assessment. This study also provided the advantages and limitations of each individual portable instrument and therefore results from this study can be used by industrial hygienists and safety professionals, with appropriate caution, when selecting a suitable portable instrument for aerosol particle measurement in nanotechnology workplaces.

Differential diagnostic significance of epithelial and stromal CD10 expression in tumors of trichogenic origin

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 719-728, June 2018.

Journal‐Club

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 815-815, June 2018.

In Memoriam Professor Dr. Dr. h. c. mult. Otto Braun‐Falco

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 817-818, June 2018.

Differenzialdiagnostische Bedeutung epithelialer und stromaler CD10‐Expression in Tumoren trichogenen Ursprungs

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 719-729, June 2018.

ÖGDV Preisträger stellen sich vor: Der Österreichische Dermatologenpreis – Unilever Preis 2017 ging an Dr. Stefan Blunder aus Innsbruck

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 816-816, June 2018.

S3‐Leitlinie zur Therapie der Psoriasis vulgaris Update – Kurzfassung Teil 2 – Besondere Patientengruppen und spezielle Behandlungssituationen

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 806-814, June 2018.

Tumoren der Kopfhaut

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 730-754, June 2018.

Impact of red versus blue light on tolerability and efficacy of PDT: a randomized controlled trial

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 711-717, June 2018.

Einfluss von Rot‐ versus Blaulicht auf Verträglichkeit und Wirksamkeit der PDT: eine randomisierte kontrollierte Studie

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 711-718, June 2018.

Scalp tumors

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 730-753, June 2018.

What is psoriasis? – Perception and assessment of psoriasis among the German population

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 703-710, June 2018.

Pachyonychie eines Zehnagels bei einem Kind

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 794-797, June 2018.

Mehrere erworbene pigmentierte Läsionen bei einem Patienten mit Melanom

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 791-793, June 2018.

Erythematous atrophic, sharply demarcated plaques with comedo‐like follicular hyperkeratoses, tense blisters and crusts on the extensor aspects of the lower extremities

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 802-804, June 2018.

A case of tinea corporis on the arm caused by Nannizzia gypsea with dermatoscopic images

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 784-786, June 2018.

Pemphigoid gestationis mit letaler fötaler Fehlbildung und postpartaler Persistenz

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 775-777, June 2018.

Kutan metastasiertes Mammakarzinom bei einer Frau simuliert ein Angiosarkom am Gesicht und Hals

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 760-762, June 2018.

Langsam wachsender exophytischer hyperpigmentierter Knoten an der Wade

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue 6, Page 798-801, June 2018.

A simple cleanup method for the removal of humic substances from soil protein extracts using aluminum coagulation

Abstract

Soil proteomics, the large-scale characterization of the entire protein complement in soils, provides a promising approach for deciphering the role of microbial functioning in terrestrial ecosystems. However, the extraction of soil proteins in sufficient quantities and of adequate purity remains a challenging task mainly due to the co-extraction of interfering humic substances. Up to now, the treatment of soil extracts with liquid phenol has been the "gold standard" for reducing humics, while the NoviPure cleanup kit was recently launched as a non-toxic approach. The present study describes an alternative method for delivering high-purity proteins based on humic coagulation with trivalent aluminum ions (Al³⁺). Various experimental parameters were optimized individually in order to maximize protein yield and diminish co-extracted humics. The optimized method was applied on a set of soil samples with diverse physicochemical characteristics and a comparison with the other two techniques was conducted. The amount of residual humics resulting from Al³⁺-based method was 26 and 35% higher than that from phenol treatment and NoviPure Kit, respectively, but these differences were of marginal statistical significance. With regard to extracted proteins, the average yields of the three methods were comparable, without showing any statistically significant differences. Overall, humic coagulation with Al³⁺ offers comparable cleanup performance in terms of protein yield and purity, but it is less toxic and less complex than the phenol-partitioning method, whereas it is far less expensive than the NoviPure Kit. The new technique is expected to facilitate the implementation of proteomic studies in soils.

Erratum to The UVA-induced long non-coding RNA GS1-600G8.5 regulates the expression of IL-8, J. Dermatol. Sci. 90 June (3) (2018) 363–366

The publisher regrets 'Kazuyuki Yo; POLA Chemical Industries, Inc, Skin Research Department' was inadvertently omitted as joint first author on the manuscript and should have been listed together with Thomas M. Rünger. The publisher would like to apologise for any inconvenience caused.

Ambient air pollution of particles and gas pollutants, and the predicted health risks from long-term exposure to PM 2.5 in Zhejiang province, China

Abstract

In recent years, ambient air has been severely contaminated by particulate matters (PMs) and some gas pollutants (nitrogen dioxide (NO₂) and sulfur dioxide (SO₂)) in China, and many studies have demonstrated that exposure to these pollutants can induce great adverse impacts on human health. The concentrations of the pollutants were much higher in winter than those in summer, and the average concentrations in this studied area were lower than those in northern China. In the comparison between high-resolution emission inventory and spatial distribution of PM_2.5, significant positive linear correlation was found. Though the pollutants had similar trends, NO₂ and SO₂ delayed with 1 h to PM_2.5. Besides, PM_2.5 had a lag time of 1 h to temperature and relative humidity. Significant linear correlation was found among pollutants and meteorological conditions, suggesting the impact of meteorological conditions on ambient air pollution other than emission. For the 24-h trend, lowest concentrations of PM_2.5, NO₂, and SO₂ were found around 15:00–18:00. In 2015, the population attributable fractions (PAFs) for ischemic heart disease (IHD), cerebrovascular disease (stroke), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and acute lower respiratory infection (ALRI) due to the exposure to PM_2.5 in Zhejiang province were 25.82, 38.94, 17.73, 22.32, and 31.14%, respectively. The population-weighted mortality due to PM_2.5 exposure in Zhejiang province was lower than the average level of the whole country—China.

Oxidative stress biomarkers and organochlorine pesticides in nesting female hawksbill turtles Eretmochelys imbricata from Mexican coast (Punta Xen, Mexico)

Abstract

Because of their vulnerable population status, assessing exposure levels and impacts of toxicants on the health status of Gulf of Mexico marine turtle populations is essential, and this study was aimed to obtain baseline information on oxidative stress indicators in hawksbill sea turtle (Eretmochelys imbricata). In order to evaluate the health status of sea turtles and the effect of organochlorine compounds (OC) in the southern part of the Gulf of Mexico, we searched for relationships between carapace size and the activity of antioxidant enzymes in the blood of the hawksbill sea turtle. The level of oxidative stress biomarkers such as the enzymes catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione S-transferase (GST), and acetylcholinesterase (Ache) in the hawksbill sea turtle was analysed during nesting season in the years 2014–2015 at Punta Xen (Campeche, Mexico). The results of this study provide insight into data of antioxidant enzyme activities in relation to contaminant OCPs in hawksbill sea turtles and the possible health impacts of contaminant in sea turtles.

Removal of two anionic reactive textile dyes by adsorption into MgAl-layered double hydroxide in aqueous solutions

Abstract

Textile dyes pose a significant challenge for water pollution due to the poor degradability of their complex aromatic structures (e.g., RR-120 and RBB-150). In order to minimize the harmful effects of RR-120 and RBB-150, the capacity of MgAl-layered double hydroxide for removing of these contaminants was studied herein. Batch adsorption experiments were conducted to investigate the effect of various operating parameters, such as solution pH, contact time, dye concentration, and temperature in order to provide optimal conditions for removal. Structural and morphological analyses were used to highlight the assembly and/or interaction LDH-dye. The state of equilibrium of RR-120 and RBB-150 adsorption was pH- and temperature-dependent and followed the pseudo-second-order rate model. Also, the equilibrium adsorption data of both dyes were found to adopt the Langmuir type isotherm model, which assumes a monolayer arrangement in LDH-dye. Furthermore, the effects of four major coexisting and competing mono- and divalent interlayer anions, such as NO₃⁻, Cl⁻, CO₃²⁻, and SO₄²⁻, on the uptakes of RR-120 and RBB-150 were studied and the results showed that NO₃⁻ anions had insignificant effect on the uptakes of RR-120 and RBB-150 by MgAl. An equivalent study on the presence of both dyes in competitive trial adsorption/desorption from binary aqueous solution was investigated. And finally, the reuse operation of recovered material after dye adsorption was tested in up to 5 cycles of recyclability.

Role of Retrobulbar Hyaluronidase in Filler-Associated Blindness: Evaluation of Fundus Perfusion and Electroretinogram Readings in an Animal Model

Purpose: Hyaluronic acid gel filler-associated blindness is an uncommon but devastating complication. Hyaluronidase can potentially dissolve intravascular filler and improve perfusion; however, its role in filler-associated blindness has yet to be determined. The purpose of this study is to determine the effect of retrobulbar hyaluronidase on hyaluronic acid gel-induced ophthalmic artery occlusion in a rabbit model. Methods: New Zealand red rabbits were used to simulate hyaluronic acid gel filler-associated vascular occlusive blindness. Ophthalmic artery occlusion and subsequent ischemia were confirmed by both retinal fundus photography and electroretinogram changes. Retrobulbar hyaluronidase 1,000 IU was injected 30 minutes after occlusion. Fundus photography and electroretinogram changes were recorded at 30, 60, 90, and 120 after administration of retrobulbar hyaluronidase. Results: A total of 6 rabbits were used, for a total of 12 eyes. Four eyes were used as controls. Of the 8 experimental eyes, 2 eyes had recorded partial occlusion and 6 eyes had fully occluded ophthalmic arteries by angiographic evaluation. One of the partially occluded eyes demonstrated some improvement in perfusion 60 minutes after injection of retrobulbar hyaluronidase; however, electroretinogram readings remained flat over the 120-minute period of observation. Six eyes with completely occluded ophthalmic arteries showed no improvement in retinal perfusion with corresponding flat electroretinogram readings at 120 minutes following retrobulbar hyaluronidase injection. Conclusions: In this rabbit model, 1,000 IU of retrobulbar hyaluronidase administered 30 minutes after occlusion failed to reverse obstruction or restore function following hyaluronic acid gel occlusion of the ophthalmic artery. Accepted for publication March 25, 2018. Presented at American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS), Chicago IL, October 2016. Supported by Jerome Comet Klein MD Foundation. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Catherine J. Hwang, M.D., Cleveland Clinic Foundation, Cole Eye Institute, 9500 Euclid Ave, i-20, Cleveland, OH 44195. E-mail: hwangc2@ccf.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Change in Eyelid Carcinoma T Category With Use of the 8th Versus 7th Edition of the American Joint Committee on Cancer: Cancer Staging Manual

Purpose: To evaluate the frequency and nature of changes in T category when eyelid carcinomas are staged using the criteria in the 8th edition instead of the 7th edition of the American Joint Committee on Cancer staging manual. Methods: Following Institutional Review Board approval, a retrospective review was conducted for all consecutive patients with the diagnosis of eyelid carcinoma treated by the senior author from January 2012 through December 2016. After a review of the clinical and pathologic data, each patient's disease was staged using both the 7th-edition and 8th-edition American Joint Committee on Cancer criteria for eyelid carcinomas. Changes in T categories between the 2 staging systems were examined. Results: The review initially identified 167 patients with the diagnosis of eyelid carcinoma. Four patients were excluded because of incomplete or unclear data. The remaining 163 patients included 78 men and 85 women aged 21 to 97 years (median, 68 years). Eighty-two patients had basal cell carcinoma; 35, squamous cell carcinoma; 32, sebaceous carcinoma; 6, mucinous eccrine carcinoma; 3, Merkel cell carcinoma; 3, adenocarcinomas; and 2, adnexal carcinoma. The most common T category according to the 7th-edition criteria was T2a; the most common T category according to the 8th-edition criteria was T1b. Of the 163 patients, 64 (39%) had a lower T category with the 8th-edition than with the 7th-edition criteria, 59 (36%) had a higher T category, and 40 (25%) had the same T category. Conclusions: Application of the 8th-edition American Joint Committee on Cancer criteria for eyelid carcinoma changed the T category in 75% of patients. In general, the new 8th-edition American Joint Committee on Cancer tumor, node, metastasis (TNM) designations allow for a more objective and consistent designation of the T category. Accepted for publication March 25, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Bita Esmaeli, M.D., F.A.C.S., Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1488, Houston, TX 77030. E-mail: besmaeli@mdanderson.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Issue Information

Contact Dermatitis, Volume 79, Issue 1, Page i-i, July 2018.

Contact dermatitis caused by diltiazem cream and cross‐reactivity with other calcium channel blockers

Contact Dermatitis, EarlyView.

Extended documentation for hand dermatitis patients: Pilot study on irritant exposures

Contact Dermatitis, EarlyView.

Methylisothiazolinone contact allergy in Croatia: Epidemiology and course of disease following patch testing

Contact Dermatitis, EarlyView.

Contact dermatitis caused by a green permanent marker

Contact Dermatitis, EarlyView.

Solvent Orange 60 is a potent contact sensitizer in occupational and everyday life

Contact Dermatitis, EarlyView.

Severe allergic contact dermatitis mimicking angioedema caused by propolis used as a traditional remedy

Contact Dermatitis, EarlyView.

Systemic allergic dermatitis caused by disulfiram (Antabuse) in a patient previously sensitized to rubber accelerators

Contact Dermatitis, EarlyView.

Positive patch test reaction to carbamazepine after a very long delay

Contact Dermatitis, EarlyView.

Low‐dose weekly methotrexate used to treat cutaneous Rosai–Dorfman disease

Clinical and Experimental Dermatology, EarlyView.

An unusual case of multiple nodules on the lower legs

Clinical and Experimental Dermatology, EarlyView.

Cutaneous metastasis in a patient with multiple malignancies

Clinical and Experimental Dermatology, EarlyView.

Rickets re‐emerging: a cautionary tale

Clinical and Experimental Dermatology, EarlyView.

Bilirubin oxidation derived from oxidative stress is associated with disease severity of atopic dermatitis in adults

Clinical and Experimental Dermatology, EarlyView.

Elevated serum eosinophil cationic protein and transforming growth factor‐α levels in a patient with pemphigus vegetans

Clinical and Experimental Dermatology, EarlyView.

Subclinical atherosclerosis in psoriasis: a clue to aortic abnormalities?

Clinical and Experimental Dermatology, EarlyView.

Leucoderma on the lips induced by neem (Azadirachta indica): case series

Clinical and Experimental Dermatology, EarlyView.

A simple, safe and cheap treatment of eccrine hidrocystomas: topical aluminium hexachloride

Clinical and Experimental Dermatology, EarlyView.

Intravenous immunoglobulin is an effective treatment for refractory cutaneous dermatomyositis

Clinical and Experimental Dermatology, EarlyView.

Association between climate, pollution and hospitalization for pemphigus in the USA

Clinical and Experimental Dermatology, EarlyView.

Malnutrition and skin disease in Far East prisoners‐of‐war in World War II

Clinical and Experimental Dermatology, EarlyView.

Methotrexate‐associated lymphoproliferative disorder presenting as giant ulcers on the leg

Clinical and Experimental Dermatology, EarlyView.

Cutaneous metastases of melanoma presenting as sudden haematomas: clinical, dermoscopic and sonographic features

Clinical and Experimental Dermatology, EarlyView.

Intravascular basal cell carcinoma: what to do next?

Clinical and Experimental Dermatology, EarlyView.

A small nodule on the auricle

Clinical and Experimental Dermatology, EarlyView.

Acneiform follicular mucinosis: an indolent follicular mucinosis variant unrelated to mycosis fungoides?

Clinical and Experimental Dermatology, EarlyView.

Pityriasis rubra pilaris‐like erythroderma secondary to phosphoinositide 3‐kinase inhibition

Clinical and Experimental Dermatology, EarlyView.

Febrile ulceronecrotic Mucha–Habermann disease after levamisole‐adulterated cocaine use: an unusual case

Clinical and Experimental Dermatology, EarlyView.

Perianal nodule in a young woman

Clinical and Experimental Dermatology, EarlyView.

Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.

SIGNIFICANCE STATEMENT BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD.

Region- and Activity-Dependent Regulation of Extracellular Glutamate

Transporter-mediated glutamate uptake plays an essential role in shaping synaptic neurotransmission. The rapid removal of synaptically released glutamate ensures the high temporal dynamics characteristic of fast excitatory chemical neurotransmission and prevents the overexcitation of extrasynaptic NMDA receptors that have been implicated in synaptic plasticity impairments and cell death. Despite clear regional differences in plasticity and excitotoxic thresholds, few studies have compared extracellular glutamate dynamics across different brain regions and in response to a range of neural activity including plasticity-inducing stimuli. Here, we used the rapid extracellular fluorescent glutamate sensor iGluSnFR (intensity-based glutamate-sensing fluorescent reporter) and high-speed imaging (205 frames per second) to quantify relative differences in glutamate clearance rates over a wide range of presynaptic activity in situ in the hippocampus, cortex, and striatum of male C57/BL6NCrl mice. We found that the hippocampus was significantly more efficient than the cortex and striatum at clearing synaptically released glutamate and that this efficiency could be attributed, at least in part, to faster glutamate diffusion away from the release site. In addition, we found that pharmacological inhibition of GLT-1, the brain's most abundant glutamate transporter, slowed clearance rates to only a fraction (~20–25%) of the effect induced by nonselective transporter blockade, regardless of the brain region and the duration of presynaptic activity. In all, our data reveal clear regional differences in glutamate dynamics after neural activity and suggest that non-GLT-1 transporters can make a large contribution to the rate of glutamate clearance in the hippocampus, cortex, and striatum.

SIGNIFICANCE STATEMENT Glutamate is the brain's most abundant neurotransmitter, and although essential for rapid cell–cell communication, too much glutamate can negatively impact cellular health. Extracellular glutamate levels are tightly regulated by membrane-bound transporters that rapidly remove the glutamate that is released during neural activity, thereby shaping both the spatial and temporal dynamics of excitatory neurotransmission. Using high-speed imaging of an optical sensor of extracellular glutamate, we show that glutamate dynamics vary widely from one brain region to the next and are highly dependent on the duration of synaptic activity. Our data demonstrate the heterogeneous nature of glutamate regulation in the brain and suggest that such regional differences can dramatically affect both the localization and duration of postsynaptic receptor activation during synaptic neurotransmission.

The Dorsal Wave of Neocortical Oligodendrogenesis Begins Embryonically and Requires Multiple Sources of Sonic Hedgehog

Neural progenitor cells in the developing dorsal forebrain give rise to excitatory neurons, astrocytes, and oligodendrocytes for the neocortex. While we are starting to gain a better understanding about the mechanisms that direct the formation of neocortical neurons and astrocytes, far less is known about the molecular mechanisms that instruct dorsal forebrain progenitors to make oligodendrocytes. In this study, we show that Sonic hedgehog (Shh) signaling is required in dorsal progenitors for their late embryonic transition to oligodendrogenesis. Using genetic lineage-tracing in mice of both sexes, we demonstrate that most oligodendrocytes in the embryonic neocortex derive from Emx1⁺ dorsal forebrain progenitors. Deletion of the Shh signaling effector Smo specifically in Emx1⁺ progenitors led to significantly decreased oligodendrocyte numbers in the embryonic neocortex. Conversely, knock-out of the Shh antagonist Sufu was sufficient to increase neocortical oligodendrogenesis. Using conditional knock-out strategies, we found that Shh ligand is supplied to dorsal progenitors through multiple sources. Loss of Shh from Dlx5/6⁺ interneurons caused a significant reduction in oligodendrocytes in the embryonic neocortex. This phenotype was identical to that observed upon Shh deletion from the entire CNS using Nestin-Cre, indicating that interneurons migrating into the neocortex from the subpallium are the primary neural source of Shh for dorsal oligodendrogenesis. Additionally, deletion of Shh from migrating interneurons together with the choroid plexus epithelium led to a more severe loss of oligodendrocytes, suggesting that the choroid plexus is an important non-neural source of Shh ligand. Together, our studies demonstrate that the dorsal wave of neocortical oligodendrogenesis occurs earlier than previously appreciated and requires highly regulated Shh signaling from multiple embryonic sources.

SIGNIFICANCE STATEMENT Most neocortical oligodendrocytes are made by neural progenitors in the dorsal forebrain, but the mechanisms that specify this fate are poorly understood. This study identifies Sonic hedgehog (Shh) signaling as a critical pathway in the transition from neurogenesis to oligodendrogenesis in dorsal forebrain progenitors during late embryonic development. The timing of this neuron-to-glia "switch" coincides with the arrival of migrating interneurons into the dorsal germinal zone, which we identify as a critical source of Shh ligand, which drives oligodendrogenesis. Our data provide evidence for a new model in which Shh signaling increases in the dorsal forebrain late in embryonic development to provide a temporally regulated mechanism that initiates the third wave of neocortical oligodendrogenesis.

Premotor Neuron Divergence Reflects Vocal Evolution

To identify mechanisms of behavioral evolution, we investigated the hindbrain circuit that generates distinct vocal patterns in two closely related frog species. Male Xenopus laevis and Xenopus petersii produce courtship calls that include a fast trill: trains of ~60 Hz sound pulses. Although fast trill rates are similar, X. laevis fast trills have a longer duration and period than those of X. petersii. To pinpoint the neural basis of these differences, we used whole-cell patch-clamp recordings in a key premotor hindbrain nucleus (the Xenopus parabrachial area, PB_X) in ex vivo brains that produce fictive vocalizations, vocal nerve activity corresponding to advertisement call patterns. We found two populations of PB_X neurons with distinct properties: fast trill neurons (FTNs) and early vocal neurons (EVNs). FTNs, but not EVNs, appear to be intrinsically tuned to produce each species' call patterns because: (1) X. laevis FTNs generate longer and slower depolarizations than X. petersii FTNs during their respective fictive vocalizations, (2) current steps in FTNs induce burst durations that are significantly longer in X. laevis than X. petersii, and (3) synaptically isolated FTNs oscillate in response to NMDA in a species-specific manner: longer and slower in X. laevis than in X. petersii. Therefore, divergence of premotor neuron membrane properties is a strong candidate for generating vocal differences between species.

SIGNIFICANCE STATEMENT The vertebrate hindbrain includes multiple neural circuits that generate rhythmic behaviors including vocalizations. Male African clawed frogs produce courtship calls that are unique to each species and differ in temporal patterns. Here, we identified two functional subtypes of neurons located in the parabrachial nucleus: a hindbrain region implicated in vocal and respiratory control across vertebrates. One of these neuronal subtypes exhibits distinct properties across species that can account for the evolutionary divergence of song patterns. Our results suggest that changes to this group of neurons during evolution may have had a major role in establishing novel behaviors in closely related species.

Corticosterone Signaling and a Lateral Habenula-Ventral Tegmental Area Circuit Modulate Compulsive Self-Injurious Behavior in a Rat Model

Self-injurious behavior (SIB) is commonly observed in patients with neuropsychiatric disorders, as well as in nonclinical populations with stress-related mental-health problems. However, the exact circuitry mechanisms underlying SIB have remained poorly understood. Here, with bilateral injection of muscimol into the entopeduncular nucleus (EP), we established a rat model of SIB. Following the muscimol injection, the male rats exhibited in a dose-dependent manner stereotypic self-biting behavior that lasted for hours and often resulted in wounds of various severities. The SIB was associated with an elevated level of serum corticosterone and could be exacerbated by enhancing the corticosterone signaling and, conversely, alleviated by inhibiting the corticosterone signaling. Activity mapping using c-fos immunostaining, combined with connectivity mapping using herpes simplex virus-based anterograde tracing from the EP and pseudorabies virus-based retrograde tracing from the masseter muscle, revealed the potential involvement of many brain areas in SIB. In particular, the lateral habenula (LHb) and the ventral tegmental area (VTA), the two connected brain areas involved in stress response and reward processing, showed a significant increase in neuronal activation during SIB. Furthermore, suppressing the LHb activity or modulating the GABAergic transmission in the VTA could significantly reduce the occurrence of SIB. These results demonstrate the importance of stress hormone signaling and the LHb–VTA circuit in modulating SIB resulting from EP malfunction, and suggest potential targets for therapeutic intervention of SIB and related disorders.

SIGNIFICANCE STATEMENT Self-injurious behavior (SIB) occurs in ~4% of the general population, with substantially higher occurrence among adolescents and patients of neuropsychiatric disorders. Stress has been linked to the occurrence of SIB, yet the underlying mechanisms have remained unclear. Using a rat model of SIB induced by disruption of activity in the entopeduncular nucleus (EP), we found that the behavior is regulated by stress and linked to corticosterone signaling. Viral tracing and c-fos immunostaining revealed the involvement of various subcortical areas, especially the EP–lateral habenula (LHb)–ventral tegmental area (VTA) circuit, in SIB. Furthermore, regulating activity in the LHb or the VTA alleviates SIB. These results may have implications in the development of new strategies for treating SIB.

Induction and Quantification of Excitability Changes in Human Cortical Networks

How does human brain stimulation result in lasting changes in cortical excitability? Uncertainty on this question hinders the development of personalized brain stimulation therapies. To characterize how cortical excitability is altered by stimulation, we applied repetitive direct electrical stimulation in eight human subjects (male and female) undergoing intracranial monitoring. We evaluated single-pulse corticocortical-evoked potentials (CCEPs) before and after repetitive stimulation across prefrontal (n = 4), temporal (n = 1), and motor (n = 3) cortices. We asked whether a single session of repetitive stimulation was sufficient to induce excitability changes across distributed cortical sites. We found a subset of regions at which 10 Hz prefrontal repetitive stimulation resulted in both potentiation and suppression of excitability that persisted for at least 10 min. We then asked whether these dynamics could be modeled by the prestimulation connectivity profile of each subject. We found that cortical regions (1) anatomically close to the stimulated site and (2) exhibiting high-amplitude CCEPs underwent changes in excitability following repetitive stimulation. We demonstrate high accuracy (72–95%) and discriminability (81–99%) in predicting regions exhibiting changes using individual subjects' prestimulation connectivity profile, and show that adding prestimulation connectivity features significantly improved model performance. The same features predicted regions of modulation following motor and temporal cortices stimulation in an independent dataset. Together, baseline connectivity profile can be used to predict regions susceptible to brain changes and provides a basis for personalizing brain stimulation.

SIGNIFICANCE STATEMENT Brain stimulation is increasingly used to treat neuropsychiatric disorders by inducing excitability changes at specific brain regions. However, our understanding of how, when, and where these changes are induced is critically lacking. We inferred plasticity in the human brain after applying electrical stimulation to the brain's surface and measuring changes in excitability. We observed excitability changes in regions anatomically and functionally closer to the stimulation site. Those in responsive regions were accurately predicted using a classifier trained on baseline brain network characteristics. Finally, we showed that the excitability changes can potentially be monitored in real-time. These results begin to fill basic gaps in our understanding of stimulation-induced brain dynamics in humans and offer pathways to optimize stimulation protocols.

Flexible Coding of Visual Working Memory Representations during Distraction

Visual working memory (VWM) recruits a broad network of brain regions, including prefrontal, parietal, and visual cortices. Recent evidence supports a "sensory recruitment" model of VWM, whereby precise visual details are maintained in the same stimulus-selective regions responsible for perception. A key question in evaluating the sensory recruitment model is how VWM representations persist through distracting visual input, given that the early visual areas that putatively represent VWM content are susceptible to interference from visual stimulation.

To address this question, we used a functional magnetic resonance imaging inverted encoding model approach to quantitatively assess the effect of distractors on VWM representations in early visual cortex and the intraparietal sulcus (IPS), another region previously implicated in the storage of VWM information. This approach allowed us to reconstruct VWM representations for orientation, both before and after visual interference, and to examine whether oriented distractors systematically biased these representations. In our human participants (both male and female), we found that orientation information was maintained simultaneously in early visual areas and IPS in anticipation of possible distraction, and these representations persisted in the absence of distraction. Importantly, early visual representations were susceptible to interference; VWM orientations reconstructed from visual cortex were significantly biased toward distractors, corresponding to a small attractive bias in behavior. In contrast, IPS representations did not show such a bias. These results provide quantitative insight into the effect of interference on VWM representations, and they suggest a dynamic tradeoff between visual and parietal regions that allows flexible adaptation to task demands in service of VWM.

SIGNIFICANCE STATEMENT Despite considerable evidence that stimulus-selective visual regions maintain precise visual information in working memory, it remains unclear how these representations persist through subsequent input. Here, we used quantitative model-based fMRI analyses to reconstruct the contents of working memory and examine the effects of distracting input. Although representations in the early visual areas were systematically biased by distractors, those in the intraparietal sulcus appeared distractor-resistant. In contrast, early visual representations were most reliable in the absence of distraction. These results demonstrate the dynamic, adaptive nature of visual working memory processes, and provide quantitative insight into the ways in which representations can be affected by interference. Further, they suggest that current models of working memory should be revised to incorporate this flexibility.

This Week in The Journal

Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice

Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo. Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing.

SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional knock-out mouse, we performed multiple regional/cell-type-specific manipulation of RARα expression in the postnatal brain, and show that RARα signaling contributes to normal whisker-dependent texture discrimination as well as regulating spine dynamics of apical dendrites from layer (L5) pyramidal neurons in S1. Deletion of RARα in excitatory neurons in the forebrain induces elevated spine elimination and impaired sensory discrimination. Our study provides novel insights into the role of RARα signaling in cortical processing and experience-dependent spine maturation.

Synaptic Release of Acetylcholine Rapidly Suppresses Cortical Activity by Recruiting Muscarinic Receptors in Layer 4

Cholinergic afferents from the basal forebrain (BF) can influence cortical activity on rapid time scales, enabling sensory information processing and exploratory behavior. However, our understanding of how synaptically released acetylcholine (ACh) influences cellular targets in distinct cortical layers remains incomplete. Previous studies have shown that rapid changes in cortical dynamics induced by phasic BF activity can be mediated by the activation of nicotinic ACh receptors (nAChRs) expressed in distinct types of GABAergic interneurons. In contrast, muscarinic ACh receptors (mAChRs) are assumed to be involved in slower and more diffuse ACh signaling following sustained increases in afferent activity. Here, we examined the mechanisms underlying fast cholinergic control of cortical circuit dynamics by pairing optical stimulation of cholinergic afferents with evoked activity in somatosensory cortical slices of mice of either sex. ACh release evoked by single stimuli led to a rapid and persistent suppression of cortical activity, mediated by mAChRs expressed in layer 4 and to a lesser extent, by nAChRs in layers 1–3. In agreement, we found that cholinergic inputs to layer 4 evoked short-latency and long-lasting mAChR-dependent inhibition of the large majority of excitatory neurons, whereas inputs to layers 1–3 primarily evoked nAChR-dependent excitation of different classes of interneurons. Our results indicate that the rapid cholinergic control of cortical network dynamics is mediated by both nAChRs and mAChRs-dependent mechanisms, which are expressed in distinct cortical layers and cell types.

SIGNIFICANCE STATEMENT Acetylcholine (ACh) release from basal forebrain (BF) afferents to cortex influences a variety of cognitive functions including attention, sensory processing, and learning. Cholinergic control occurs on the time scale of seconds and is mediated by BF neurons that generate action potentials at low rates, indicating that ACh acts as a point-to-point neurotransmitter. Our findings highlight that even brief activation of cholinergic afferents can recruit both nicotinic and muscarinic ACh receptors expressed in several cell types, leading to modulation of cortical activity on distinct time scales. Furthermore, they indicate that the initial stages of cortical sensory processing are under direct cholinergic control.

USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels

Mutations or altered protein levels of SHANK3 are implicated in neurodevelopmental disorders such as Phelan–McDermid syndrome, autism spectrum disorders, and schizophrenia (Guilmatre et al., 2014). Loss of SHANK3 in mouse models results in decreased synapse density and reduction in the levels of multiple synaptic proteins (Jiang and Ehlers, 2013). The family of SHANK scaffolding molecules are among the most heavily ubiquitinated proteins at the postsynaptic density. The ubiquitin-dependent proteasome degradation of SHANK is regulated by synaptic activity and may contribute to activity-dependent synaptic remodeling (Ehlers, 2003; Shin et al., 2012). However, the identity of the specific deubiquitinating enzymes and E3 ligases that regulate SHANK ubiquitination at synapses are unknown. Here we identify USP8/UBPY as a deubiquitinating enzyme that regulates SHANK3 and SHANK1 ubiquitination and protein levels. In primary rat neurons, USP8 enhances SHANK3 and SHANK1 protein levels via deubiquitination and increases dendritic spine density. Additionally, USP8 is essential for changes in SHANK3 protein levels following synaptic activity modulation. These data identify USP8 as a key modulator of SHANK3 downstream of synaptic activity.

SIGNIFICANCE STATEMENT Precise regulation of the protein levels of the postsynaptic scaffolding protein SHANK3 is essential for proper neurodevelopment. Mutations of SHANK3 have been identified in Phelan–McDermid syndrome, autism spectrum disorders, and schizophrenia (Guilmatre et al., 2014). In this research, we identify USP8 as a key enzyme that regulates SHANK3 protein levels in neurons. USP8 acts to deubiquitinate SHANK3, which prevents its proteasomal-mediated degradation and enhances overall dendritic spine stability. In the future, the modulation of USP8 deubiquitinating activity could potentially be used to titrate the protein levels of SHANK3 to ameliorate disease.

Epigenetic Promoter DNA Methylation of miR-124 Promotes HIV-1 Tat-Mediated Microglial Activation via MECP2-STAT3 Axis

The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B, which were also accompanied by increased global DNA methylation. Bisulfite-converted genomic DNA sequencing in the HIV-1 Tat-exposed mouse primary microglial cells further confirmed increased DNA methylation of the primary miR-124-1 and primary miR-124-2 promoters. Bioinformatic analyses identified MECP2 as a novel 3'-UTR target of miR-124. This was further validated in mouse primary microglial cells wherein HIV-1 Tat-mediated downregulation of miR-124 resulted in increased expression of MECP2, leading in turn to further repression of miR-124 via the feedback loop. In addition to MECP2, miR-124 also modulated the levels of STAT3 through its binding to the 3'-UTR, leading to microglial activation. Luciferase assays and Ago2 immunoprecipitation determined the direct binding between miR-124 and 3'-UTR of both MECP2 and STAT3. Gene silencing of MECP2 and DNMT1 and overexpression of miR-124 blocked HIV-1 Tat-mediated downregulation of miR-124 and microglial activation. In vitro findings were also confirmed in the basal ganglia of SIV-infected rhesus macaques (both sexes). In summary, our findings demonstrate a novel mechanism of HIV-1 Tat-mediated activation of microglia via downregulation of miR-124, leading ultimately to increased MECP2 and STAT3 signaling.

SIGNIFICANCE STATEMENT Despite the effectiveness of combination antiretroviral therapy in controlling viremia, the CNS continues to harbor viral reservoirs. The persistence of low-level virus replication leads to the accumulation of early viral proteins, including HIV-1 Tat protein. Understanding the epigenetic/molecular mechanism(s) by which viral proteins, such as HIV-1 Tat, can activate microglia is thus of paramount importance. This study demonstrated that HIV-1 Tat-mediated DNA methylation of the miR-124 promoter leads to its downregulation with a concomitant upregulation of the MECP2-STAT3-IL6, resulting in microglial activation. These findings reveal an unexplored epigenetic/molecular mechanism(s) underlying HIV-1 Tat-mediated microglial activation, thereby providing a potential target for the development of therapeutics aimed at ameliorating microglial activation and neuroinflammation in the context of HIV-1 infection.

Region-Specific Regulation of Presynaptic Dopamine Homeostasis by D2 Autoreceptors Shapes the In Vivo Impact of the Neuropsychiatric Disease-Associated DAT Variant Val559

Disruptions of dopamine (DA) signaling contribute to a broad spectrum of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), addiction, bipolar disorder, and schizophrenia. Despite evidence that risk for these disorders derives from heritable variation in DA-linked genes, a better understanding is needed of the molecular and circuit context through which gene variation drives distinct disease traits. Previously, we identified the DA transporter (DAT) variant Val559 in subjects with ADHD and established that the mutation supports anomalous DAT-mediated DA efflux (ADE). Here, we demonstrate that region-specific contributions of D₂ autoreceptors (D2AR) to presynaptic DA homeostasis dictate the consequences of Val559 expression in adolescent male mice. We show that activation of D2ARs in the WT dorsal striatum (DS), but not ventral striatum (VS), increases DAT phosphorylation and surface trafficking. In contrast, the activity of tyrosine hydroxylase (TH) is D2AR-dependent in both regions. In the DS but not VS of Val559 mice, tonic activation of D2ARs drives a positive feedback loop that promotes surface expression of efflux-prone DATs, raising extracellular DA levels and overwhelming DAT-mediated DA clearance capacity. Whereas D2ARs that regulate DAT are tonically activated in the Val559 DS, D2ARs that regulate TH become desensitized, allowing maintenance of cytosolic DA needed to sustain ADE. Together with prior findings, our results argue for distinct D2AR pools that regulate DA synthesis versus DA release and inactivation and offer a clear example of how the penetrance of gene variation can be limited to a subset of expression sites based on differences in intersecting regulatory networks.

SIGNIFICANCE STATEMENT Altered dopamine (DA) signaling has been linked to multiple neuropsychiatric disorders. In an effort to understand and model disease-associated DAergic disturbances, we previously screened the DA transporter (DAT) in subjects with attention-deficit hyperactivity disorder (ADHD) and identified multiple, functionally impactful, coding variants. One of these variants, Val559, supports anomalous DA efflux (ADE) and in transgenic mice leads to changes in locomotor patterns, psychostimulant sensitivity, and impulsivity. Here, we show that the penetrance of Val559 ADE is dictated by region-specific differences in how presynaptic D₂-type autoreceptors (D2ARs) constrain DA signaling, biasing phenotypic effects to dorsal striatal projections. The Val559 model illustrates how the impact of genetic variation underlying neuropsychiatric disorders can be shaped by the differential engagement of synaptic regulatory mechanisms.

Modulation of Receptor Protein Tyrosine Phosphatase Sigma Increases Chondroitin Sulfate Proteoglycan Degradation through Cathepsin B Secretion to Enhance Axon Outgrowth

Severed axon tips reform growth cones following spinal cord injury that fail to regenerate, in part, because they become embedded within an inhibitory extracellular matrix. Chondroitin sulfate proteoglycans (CSPGs) are the major axon inhibitory matrix component that is increased within the lesion scar and in perineuronal nets around deafferented neurons. We have recently developed a novel peptide modulator (intracellular sigma peptide) of the cognate receptor of CSPGs, protein tyrosine phosphatase (RPTP), which has been shown to markedly improve sensorimotor function, micturition, and coordinated locomotor behavior in spinal cord contused rats. However, the mechanism(s) underlying how modulation of RPTP mediates axon outgrowth through inhibitory CSPGs remain unclear. Here, we describe how intracellular sigma peptide modulation of RPTP induces enhanced protease Cathepsin B activity. Using DRG neurons from female Sprague Dawley rats cultured on an aggrecan/laminin spot assay and a combination of biochemical techniques, we provide evidence suggesting that modulation of RPTP regulates secretion of proteases that, in turn, relieves CSPG inhibition through its digestion to allow axon migration though proteoglycan barriers. Understanding the mechanisms underlying RPTP modulation elucidates how axon regeneration is impaired by proteoglycans but can then be facilitated following injury.

SIGNIFICANCE STATEMENT Following spinal cord injury, chondroitin sulfate proteoglycans (CSPGs) upregulate and potently inhibit axon regeneration and functional recovery. Protein tyrosine phosphatase (RPTP) has been identified as a critical cognate receptor of CSPGs. We have previously characterized a synthetic peptide (intracellular sigma peptide) that targets the regulatory intracellular domain of the receptor to allow axons to regenerate despite the presence of CSPGs. Here, we have found that one important mechanism by which peptide modulation of the receptor enhances axon outgrowth is through secretion of a protease, Cathepsin B, which enables digestion of CSPGs. This work links protease secretion to the CSPG receptor RPTP for the first time with implications for understanding the molecular mechanisms underlying neural regeneration and plasticity.

SNT-1 Functions as the Ca2+ Sensor for Tonic and Evoked Neurotransmitter Release in Caenorhabditis Elegans

Synaptotagmin-1 (Syt1) binds Ca²⁺ through its tandem C2 domains (C2A and C2B) and triggers Ca²⁺-dependent neurotransmitter release. Here, we show that snt-1, the homolog of mammalian Syt1, functions as the Ca²⁺ sensor for both tonic and evoked neurotransmitter release at the Caenorhabditis elegans neuromuscular junction. Mutations that disrupt Ca²⁺ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca²⁺ binding in a single C2 domain had no effect, indicating that the Ca²⁺ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca²⁺ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca²⁺ entry.

SIGNIFICANCE STATEMENT We showed that SNT-1 in Caenorhabditis elegans regulates evoked neurotransmitter release through Ca²⁺ binding to its C2B domain in a similar way to Syt1 in the mouse CNS and the fly neuromuscular junction. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca²⁺-binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature EPSC, indicating that SNT-1 also acts as a Ca²⁺ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated.

Reciprocal Negative Regulation Between Lmx1a and Lmo4 Is Required for Inner Ear Formation

LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes that they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TFs, these proteins do not bind DNA directly. LMO proteins are negative regulators of LIM-TFs and function by competing with LIM-TFs for binding to Ldb's. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knock-out embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning. In addition, we have found that the reciprocal interaction between Lmx1a and Lmo4 (a LMO protein within the inner ear) mediates the formation of both vestibular and auditory structures. Lmo4 negatively regulates Lmx1a to form the three sensory cristae, the anterior semicircular canal, and the shape of the utricle in the vestibule. Furthermore, this negative regulation blocks ectopic sensory formation in the cochlea. In contrast, Lmx1a negatively regulates Lmo4 in mediating epithelial resorption of the canal pouch, which gives rise to the anterior and posterior semicircular canals. We also found that Lmx1a is independently required for the formation of the endolymphatic duct and hair cells in the basal cochlear region.

SIGNIFICANCE STATEMENT The mammalian inner ear is a structurally complex organ responsible for detecting sound and maintaining balance. Failure to form the intricate 3D structure of this organ properly during development most likely will result in sensory deficits on some level. Here, we provide genetic evidence that a transcription factor, Lmx1a, interacts with its negative regulator, Lmo4, to pattern various vestibular and auditory components of the mammalian inner ear. Identifying these key molecules that mediate formation of this important sensory organ will be helpful for designing strategies and therapeutics to alleviate hearing loss and balance disorders.

Change of signs, symptoms and voice quality evaluations throughout a 3‐ to 6‐month empirical treatment for laryngopharyngeal reflux disease

Clinical Otolaryngology, EarlyView.

Role of local anaesthetic nerve block in endoscopic sinus surgery: A systematic review and meta‐analysis

Clinical Otolaryngology, EarlyView.

Impact of age on survival of locoregional nasopharyngeal carcinoma: An analysis of the Surveillance, Epidemiology, and End Results program database, 2004‐2013

Clinical Otolaryngology, EarlyView.

A meta‐analysis on the surgical management of paraganglioma of the carotid body per Shamblin class

Clinical Otolaryngology, EarlyView.

A patient‐centred multidomain instrument for improving the clarity of outcomes reporting and documentation in complex airway surgery

Clinical Otolaryngology, EarlyView.

Primary versus secondary tracheoesophageal puncture for voice rehabilitation in laryngectomy patients: A systematic review

Clinical Otolaryngology, EarlyView.

Individual Funding Requests: A flawed process

Clinical Otolaryngology, EarlyView.

Oxford radiographic chart of foreign bodies

Clinical Otolaryngology, EarlyView.

Minimally invasive surgery for superior semicircular canal dehiscence: Results of a four fenestration technique in twenty‐one adults

Clinical Otolaryngology, EarlyView.

Nasopharyngeal versus hypopharyngeal packing during sino‐nasal surgeries: Randomised controlled trial

Clinical Otolaryngology, EarlyView.

Trends in the prescribing of topical nasal agents Using an NHS England data base

Clinical Otolaryngology, EarlyView.

Pain, psychiatric comorbidities, and psychosocial stressors associated with Klippel-Trenaunay Syndrome

Publication date: Available online 5 June 2018
Source:Journal of the American Academy of Dermatology
Author(s): Jamison A. Harvey, Henry Nguyen, Katelyn R. Anderson, Jennifer J. Schoch, Emily C. Bendel, David J. Driscoll, Brian A. Palmer, Megha M. Tollefson
BackgroundKlippel-Trenaunay syndrome (KTS) is characterized by the triad of capillary malformation (CM), venous malformation (VM) +/- lymphatic malformation, and limb overgrowth. Patients with KTS have lower scores in general and mental health, physical function, and quality of life than the general population.ObjectiveTo determine the prevalence of pain and psychiatric comorbidity in patients with KTS.MethodsA retrospective review of 410 patients with KTS evaluated between 1976 and 2012 was conducted to identify the presence of pain, psychiatric comorbidities, and psychosocial stressors.ResultsPain was reported by 260 patients (63.4%) and was associated with any KTS complication (p<0.0001) and VMs of the lower extremities (p=0.0008) and feet (p=0.0007). Ninety-five patients had a diagnosed psychiatric condition (23.2%), most commonly depression (15.1%) and anxiety (5.1%). Pain (p=0.0016), superficial thrombosis (p=0.0269), deep embolic/thrombotic events (p=0.0005), gastrointestinal complications (p=0.0085), genitourinary complications (p=0.0163), and CM of the hands (p=0.0040) were associated with having a psychiatric diagnosis.LimitationsRetrospective study that relied on physician detection and reporting of variables.ConclusionsPain and psychiatric conditions, particularly depression and anxiety, are common in patients with KTS. Awareness of the psychosocial impact of KTS and appropriate screening are important.

Teaser

Klippel-Trenaunay syndrome affects general and mental health, physical function, and quality of life. Pain, complications, and capillary malformation of the hands are associated with a higher risk of psychiatric illness. Patients with Klippel-Trenuanay syndrome should be screened for potential psychosocial sequelae..

UV irradiation through skin or eye reduces hippocampal neurogenesis and synaptic protein expression

Photodermatology, Photoimmunology &Photomedicine, EarlyView.

Facial exposure to ultraviolet radiation: Predicted sun protection effectiveness of various hat styles

Photodermatology, Photoimmunology &Photomedicine, EarlyView.

Ionizing radiation, but not ultraviolet radiation, induces mitotic catastrophe in mouse epidermal keratinocytes with aberrant cell cycle checkpoints

Experimental Dermatology, EarlyView.

An objective method to assess the improvements of skin texture roughness after botulinum toxin type a treatment of crow's feet

Skin Research and Technology, EarlyView.

A novel method to measure skin mechanical properties with three‐dimensional digital image correlation

Skin Research and Technology, EarlyView.

Validation of GPSkin Barrier® for assessing epidermal permeability barrier function and stratum corneum hydration in humans

Skin Research and Technology, EarlyView.

Mechanical spectroscopy and imaging of skin components in vivo: Assignment of the observed moduli

Skin Research and Technology, EarlyView.

Chain dynamics of human dermis by Thermostimulated currents: A tool for new markers of aging

Skin Research and Technology, EarlyView.

Sun Protection Among Organ Transplant Recipients After Participation in a Skin Cancer Research Study

This study investigates the use of sun protection among organ transplant recipients after participation in a skin cancer research study.

Polymorphic Erythematous Macules and Plaques With Dysesthesia

A woman in her 50s presented with a 2-year history of disseminated dermatosis involving the trunk and limbs; the dermatosis was characterized by polymorphic erythematous macules and plaques with elevated and indurated borders without evanescence to pressure. What is your diagnosis?

Hemophagocytic Lymphohistiocytosis in Cutaneous T-Cell Lymphoma

This case series examines the characteristics of cutaneous T-cell lymphoma associated with hemophagocytic lymphohistiocytosis and analyzes the presenting signs and symptoms, therapeutic options, and outcomes.

Core Outcome Sets for Psoriasis Clinical Trials

Standardized and relevant psoriasis-specific outcome measures would contribute to a better understanding of the benefits of a growing list of highly effective therapies. To this end, in this issue of JAMA Dermatology, Callis Duffin et al present the results of an effort to define core outcome sets (COSs) for clinical trials of psoriasis. Under the auspices of the International Dermatology Outcome Measures group, the authors conducted a Delphi survey and determined that the following 6 domains should be addressed in all psoriasis trials: (1) psoriatic skin manifestations (including location), (2) an investigator global assessment, (3) an evaluation of signs and symptoms of both psoriasis and psoriatic arthritis, (4) a patient global assessment of his or her condition, (5) an assessment of treatment satisfaction, and (6) a measure of health-related quality of life.

Identifying a Core Domain Set to Assess Psoriasis in Clinical Trials

This Delphi survey of patients, health care professionals, and other stakeholders identifies a core set of 6 domains that should be measured in all clinical trials for psoriasis therapies.

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.

Nivolumab versus ipilimumab in the treatment of advanced melanoma: a critical appraisal

British Journal of Dermatology, EarlyView.

Individuals with filaggrin‐related eczema and asthma have increased long‐term medication and hospital admission costs

British Journal of Dermatology, EarlyView.

Inherited pulmonary cylindromas: extending the phenotype of CYLD mutation carriers

British Journal of Dermatology, EarlyView.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water‐in‐oil emulsion in aged skin

British Journal of Dermatology, EarlyView.

Bilateral striatal necrosis and dyschromatosis symmetrica hereditaria: A–I editing efficiency of ADAR1 mutants and phenotype expression

British Journal of Dermatology, EarlyView.

Interleukin‐32 promotes detachment and activation of human Langerhans cells in a human skin explant model

British Journal of Dermatology, EarlyView.

Is depression screening in patients with acne critical?: reply from authors

British Journal of Dermatology, EarlyView.

Impacts of isopyrazam exposure on the development of early-life zebrafish ( Danio rerio )

Abstract

Isopyrazam (IPZ) is a broad spectrum succinate dehydrogenase inhibitor fungicide. Little is known about its potential ecological risks of aquatic organisms recently. The present study examined the embryonic development effects of zebrafish exposed to IPZ under static condition using a fish embryo toxicity test. The lowest observed effect concentration of IPZ was 0.025 mg/L in 4-day exposure. Developmental abnormalities, including edema, small head deformity, body deformation and decreased pigmentation, and mortality were observed in zebrafish embryos of 0.05 mg/L and higher concentrations, which shown concentration dependency. The heart rate of zebrafish was disrupted by IPZ. Moreover, enzyme and gene experiments shown that IPZ exposure caused oxidative stress of zebrafish. Furthermore, it induced a decrease of succinate dehydrogenase (SDH) enzyme activity and gene transcription level in zebrafish larvae. It can be speculated that IPZ may have a lethal effect on zebrafish, which is accompanied by decreased SDH activity, oxidative stress, and abnormality. These results provide toxicological data about the IPZ on aquatic non-target organisms, which could be useful for further understanding potential environmental risks.

Mode of action of poloxamer‐based surfactants in wound care and efficacy on biofilms

International Wound Journal, EarlyView.

Staphylococcal infection of lower leg mimicking mycetoma

International Wound Journal, EarlyView.

Skin cancers and dermal substitutes: Is it safe? Review of the literature and presentation of a 2‐stage surgical protocol for the treatment of non‐melanoma skin cancers of the head in fragile patients

International Wound Journal, EarlyView.

The application of incisional negative pressure wound therapy for perineal wounds: A systematic review

International Wound Journal, EarlyView.

Role of anaerobes in polymicrobial communities and biofilms complicating diabetic foot ulcers

International Wound Journal, EarlyView.

Effectiveness of the strategies of an orientation programme for the lifestyle and wound‐healing process in patients with venous ulcer: A randomised controlled trial

International Wound Journal, EarlyView.

An important and overlooked parameter in platelet rich plasma preparation: The mean platelet volume

Journal of Cosmetic Dermatology, EarlyView.

Cutaneous acceptability of a moisturizing cream in subjects with sensitive skin

Journal of Cosmetic Dermatology, EarlyView.

Platelet rich plasma for photodamaged skin: A pilot study

Journal of Cosmetic Dermatology, EarlyView.

Melanocyte development in the mouse tail epidermis requires the Adamts9 metalloproteinase

Pigment Cell &Melanoma Research, EarlyView.

BRN2, a POUerful driver of melanoma phenotype switching and metastasis

Pigment Cell &Melanoma Research, EarlyView.

Psoriasis Area and Severity Index response in moderate‐severe psoriatic patients switched to adalimumab: results from the OPPSA study

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Silver absorption and toxicity evaluation of silver wound dressings in 40 patients with chronic wounds

Journal of the European Academy of Dermatology and Venereology, EarlyView.

The effects of season and weather on healthcare utilization among patients with atopic dermatitis

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Trends in hospitalization rates for psoriasis flares since the introduction of biologics: a time series in France between 2005 and 2015

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population‐based study

Journal of the European Academy of Dermatology and Venereology, EarlyView.

The effect of autoimmune blistering diseases on work productivity

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Genetic polymorphism of thymic stromal lymphopoietin in Korean patients with atopic dermatitis and allergic march

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Tattoo‐associated uveitis with or without systemic sarcoidosis: a comparative review of the literature

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Presence of SCF/CXCL12 double‐positive large blast‐like cells at the site of cutaneous extramedullary haematopoiesis

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Beta‐adrenoceptor expression in pemphigus foliaceus

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Problems and challenges of predatory journals

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Outdoor environment, ozone, radionuclide‐associated aerosols and incidences of infantile eczema in Minsk, Belarus

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Drug‐induced longitudinal melanonychia and transverse muehrcke's lines

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Effectiveness of omalizumab in chronic spontaneous urticaria assessed with patient‐reported outcomes: a prospective study

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Ipilimumab more and more discussed: urgent need for predictive markers of response

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 6, Page 849-849, June 2018.

Forthcoming Events

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 6, Page 1044-1044, June 2018.

Issue Information

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 6, Page 843-848, June 2018.

Announcement

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 6, Page 1045-1045, June 2018.

Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 6, Page 850-878, June 2018.

Pseudo‐Kaposi sarcoma: report of a case investigated by dermoscopy, reflectance confocal microscopy and optical coherence tomography

Journal of the European Academy of Dermatology and Venereology, EarlyView.

Diagnostic accuracy of whole slide imaging for cutaneous, soft tissue, and melanoma sentinel lymph node biopsies with and without immunohistochemistry

Journal of Cutaneous Pathology, EarlyView.

Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site

Journal of Cutaneous Pathology, EarlyView.

Malignant melanoma with osteosarcomatous differentiation in a lymph node metastasis

Journal of Cutaneous Pathology, EarlyView.

Granulomatous dermatitis associated with ipilimumab therapy (ipilimumab associated granulomatous dermatitis)

Journal of Cutaneous Pathology, EarlyView.

Influence of variability in assessment of Breslow thickness, mitotic rate and ulceration among US pathologists interpreting invasive melanoma, for the purpose of AJCC staging

Journal of Cutaneous Pathology, EarlyView.

On the Simultaneous Identification and Quantification of Microalgae Populations Based on Fluorometric Techniques

Photochemistry and Photobiology, EarlyView.

Generation of 8‐oxo‐7,8‐dihydroguanine in G‐Quadruplexes Models of Human Telomere Sequences by One‐electron Oxidation

Photochemistry and Photobiology, EarlyView.

Photoprotective Effects of a Multifunctional Hair Care Formulation Containing Botanical Extracts, Vitamins, and UV Filters

Photochemistry and Photobiology, EarlyView.

Human‐computer symbiosis: enhancing dermatologic care while preserving the art of healing

International Journal of Dermatology, EarlyView.

Climate change and atopic dermatitis: is there a link?

International Journal of Dermatology, EarlyView.

JAK‐STAT signaling pathway inhibition: a role for treatment of discoid lupus erythematosus and dermatomyositis

International Journal of Dermatology, EarlyView.

Incidence of pemphigus vulgaris and pemphigus foliaceus in North‐East Poland (Podlaskie Province) – a 15‐year (2001–2015) bicentric retrospective study

International Journal of Dermatology, EarlyView.

Erratum

International Journal of Dermatology, EarlyView.

Acral nodule as a form of atypical presentation of a tufted angioma in adulthood

International Journal of Dermatology, EarlyView.

Psychosomatic factors of atopic dermatitis exacerbation

International Journal of Dermatology, EarlyView.

Hypohidrotic ectodermal dysplasia: clinical and molecular review

International Journal of Dermatology, EarlyView.

Disseminated tuberculosis following adalimumab treatment in psoriasis despite negative screening

International Journal of Dermatology, EarlyView.

First case of symmetrical drug‐related intertriginous and flexural exanthema (SDRIFE) due to Berberine, an over‐the‐counter herbal glycemic control agent

International Journal of Dermatology, EarlyView.

Vitamin D status in adult patients with nonmelanoma skin cancer in Cape Town, South Africa: a cross‐sectional study

International Journal of Dermatology, EarlyView.

Bazex‐Dupré‐Christol syndrome: review of clinical and molecular aspects

International Journal of Dermatology, EarlyView.

Pigmented mammary Paget disease mimicking cutaneous melanoma

International Journal of Dermatology, EarlyView.

Comorbidities in vitiligo: comprehensive review

International Journal of Dermatology, EarlyView.

A prospective study to validate various clinical criteria used in classification of leprosy: a study from a tertiary care center in India

International Journal of Dermatology, EarlyView.

Multiple red‐brown nodules and plaques on the face, trunk, and bilateral elbows

International Journal of Dermatology, EarlyView.

The rapidly evolving lesions of ulcerative pyoderma gangrenosum: a timeline

International Journal of Dermatology, EarlyView.

Colloid milium: the expanding spectrum of orange color at dermoscopy

International Journal of Dermatology, EarlyView.

Prurigo‐like herpes simplex

International Journal of Dermatology, EarlyView.

Multiple vegetating plaques on a Cesarean section scar

International Journal of Dermatology, EarlyView.

Migratory, recurrent skin eruption in a returning traveller

Australasian Journal of Dermatology, EarlyView.

Systemic contact dermatitis caused by inhalation of epoxy resin in industrial waste vapour

Australasian Journal of Dermatology, EarlyView.

Immediate irritant dermatitis from the passionvine hopper (Scolypopa australis)

Australasian Journal of Dermatology, EarlyView.

Cervicofacial subcutaneous emphysema after facial cosmetic procedure in an 11‐year‐old girl

Australasian Journal of Dermatology, EarlyView.

Chemopreventive potential of nicotinamide in Gilmore's Bayesian analysis

Australasian Journal of Dermatology, EarlyView.

Treatment of giant vulvar syringomas with topical adelmidrol: The role of mast cells

Australasian Journal of Dermatology, EarlyView.

Eosinophilic fasciitis and lichen sclerosus in a patient treated with nivolumab

Australasian Journal of Dermatology, EarlyView.

Issue Information ‐ TOC

Australasian Journal of Dermatology, Volume 59, Issue 2, Page 79-81, May 2018.

Corrigendum

Australasian Journal of Dermatology, Volume 59, Issue 2, Page 162-162, May 2018.

Issue Information ‐ JEB

Australasian Journal of Dermatology, Volume 59, Issue 2, Page 83-83, May 2018.

Issue Information

The Journal of Dermatology, Volume 45, Issue 6, Page i, 631-632, June 2018.

Corrigendum

The Journal of Dermatology, Volume 45, Issue 6, Page 751-751, June 2018.

Issue Information

The Journal of Dermatology, Volume 45, Issue 6, Page 752-752, June 2018.

Epithelial–mesenchymal transition in Bowen's disease when arising de novo and acquiring invasive capacity

The Journal of Dermatology, Volume 45, Issue 6, Page 748-750, June 2018.

Epidermal barrier disruption by 9‐hydroxy‐10E,12Z‐octadecadienoic acid in human keratinocytes

The Journal of Dermatology, Volume 45, Issue 6, Page 746-747, June 2018.

Guidelines for the diagnosis and treatment of male‐pattern and female‐pattern hair loss, 2017 version

The Journal of Dermatology, EarlyView.

Two cases of conjunctival squamous cell carcinoma in the anophthalmic socket after treatment of retinoblastoma

The Journal of Dermatology, EarlyView.

Scleroderma‐like syndrome associated with nivolumab treatment in malignant melanoma

The Journal of Dermatology, EarlyView.

Localized scleroderma occurring after treatment of chronic hepatitis C with sofosbuvir and ribavirin

The Journal of Dermatology, EarlyView.

Tubular apocrine adenoma: A rare and controversial tumor

The Journal of Dermatology, EarlyView.

pH in nature, humans and skin

The Journal of Dermatology, EarlyView.

Case of psoriasiform and pustular eruptions in addition to alopecia as a paradoxical reaction induced by infliximab

The Journal of Dermatology, EarlyView.

Nevus unius lateris: Electrofulguration as a therapeutic approach

The Journal of Dermatology, EarlyView.

Case of late‐onset focal dermal elastosis

The Journal of Dermatology, EarlyView.

Mild hyperbaric oxygen activates the proliferation of epidermal basal cells in aged mice

The Journal of Dermatology, EarlyView.

From biologic to biologic: Ulcerative colitis in the setting of psoriasis treatment

The Journal of Dermatology, EarlyView.

H syndrome: Clinical, histological and genetic investigation in Tunisian patients

The Journal of Dermatology, EarlyView.

Four cases of acute infectious urticaria showing significant elevation of plasma D‐dimer level

The Journal of Dermatology, EarlyView.

Pigmented mammary Paget's disease without underlying carcinoma

The Journal of Dermatology, EarlyView.

Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients

The Journal of Dermatology, EarlyView.

Promoting sun light-induced photocatalytic degradation of toxic phenols by efficient and stable double metal cyanide nanocubes

Abstract

Aromatic substituted phenols and their by-products discharged from numerous industries are of environmental concern due to their toxic, carcinogenic, recalcitrant, and bioaccumulating properties. Therefore, their complete removal from waters by low-cost, efficient, environmentally friendly nanomaterial-based treatment techniques is desirable. Double metal cyanide complexes (DMCC) are the extremely useful heterogeneous and recoverable catalyst. Hence, green route has been developed for several DMCC and their photocatalytic efficiency was evaluated for degradation of toxic phenols. Herein, nanocubes for hexacyanocobaltate of iron (FeHCC ~ 200 nm), nickel (NiHCC < 10 nm), and zinc (ZnHCC ~ 500 nm) were synthesized after employing Aegle marmelos. Subsequently, at neutral pH and sunlight irradiation, 15 mg of catalysts were able to degrade the maximum extent of phenols (1 × 10⁻⁴ M) in the order: 3-aminophenol (96% ZnHCC > 94% FeHCC > 93% NiHCC) > phenol (94% ZnHCC > 92% FeHCC > 91% NiHCC) > 2,4-DNP (92% ZnHCC > 91% FeHCC > 90% NiHCC). This is attributed to highest basicity of 3-aminophenol containing excess of free electrons. Highest catalytic potential of ZnHCC (X_m = 0.54–0.43 mg/g) is because of its highest surface area and negative zeta potential along with sharp morphology and crystallinity. Adsorption of phenols over catalyst was statistically significant with Langmuir isotherms (R² ≥ 0.96; p value ≤ 0.05). Small and non-toxic by-products like oxalic acid, benzoquinone, (Z)-hex-3-enedioic acid, (Z)-but-2-enal, and (Z)-4-oxobut-2-enoic acid were identified in GC-MS. Degradation modes involving hydroxylation, oxidative skeletal rearrangement, and ring opening clearly supported enhanced oxidation of phenols by ^•OH. Overall, due to greater active sites, high surface activity, low band gap, and semiconducting nature, DMCC revealed promising potential for solar photocatalytic remediation of wastewater.

Effect of multi-wall carbon nanotubes on Cr(VI) reduction by citric acid: Implications for their use in soil remediation

Abstract

The potential application of carbon nanotubes (CNTs) in waste water treatment and their effect on the fate of heavy metals in the environments have attracted wide attention. However, the influence of CNTs on the reduction of Cr(VI) to Cr(III) in soils remains unknown. In this study, Cr(VI) adsorption by carboxylated or hydroxylated multi-walled carbon nanotubes (MWCNT-COOH or MWCNT-OH) was investigated together with their catalytic effect on Cr(VI) reduction by citric acid. Across the initial concentration range examined (5–60 mg/L), the adsorption capacity of Cr(VI) by MWCNT-COOH and MWCNT-OH (pH 5.0) could reach to 8.09 and 7.85 mg/g, respectively. With the decrease in pH, the Cr(VI) adsorption by both MWCNTs increased, while their difference in adsorption capacity became more pronounced, evidenced by that the percentage of Cr(VI) adsorbed by MWCNT-COOH can be 1.3-fold higher than that of MWCNT-OH at a pH of 3.2. The Cr(VI) adsorption kinetics could be well described by pseudo-second-order (R² > 0.95) and intra-particle diffusion models (R² > 0.98). MWCNT-OH or MWCNT-COOH could accelerate the reduction of 0.1 mM Cr(VI) by 1.0 mM citric acid, with the first-order rate constant of 0.0325 and 0.0147 h⁻¹, respectively. This finding was explained as that the reactivity of citric acid might be enhanced with its adsorption on the MWCNT surfaces. The catalysis of the functionalized CNTs on the Cr(VI) reduction was inhibited as the pH increased. The addition of MWCNTs to an oxisol can enhance the Cr(VI) reduction because the final concentration of aqueous Cr(III), compared with that without addition of MWCNTs, increased from 20.7 to 32.6 μM. Meanwhile, re-adsorption of aqueous Cr(III) onto the solid surfaces was also observed. The results above are important for understanding on the effect of CNTs on the fate of Cr(VI) and how they can be used to remediate Cr(VI)-polluted soils.

Optimization of the electrochemical degradation process of the antibiotic ciprofloxacin using a double-sided β-PbO 2 anode in a flow reactor: kinetics, identification of oxidation intermediates and toxicity evaluation

Abstract

The electrochemical degradation of ciprofloxacin—CIP (50 mg L⁻¹ in 0.10 mol L⁻¹ Na₂SO₄) was investigated using a double-sided Ti-Pt/β-PbO₂ anode in a filter-press flow reactor, with identification of oxidation intermediates and follow-up of antimicrobial activity against Escherichia coli. The effect of solution pH, flow rate, current density, and temperature on the CIP removal rate was evaluated. All of these parameters did affect the CIP removal performance; thus, optimized electrolysis conditions were further explored: pH = 10, q_V  = 6.5 L min⁻¹, j = 30 mA cm⁻², and θ = 25 °C. Therefore, CIP was removed within 2 h, whereas ~75% of the total organic carbon concentration (TOC) was removed after 5 h and then, the solution no longer presented antimicrobial activity. When the electrochemical degradation of CIP was investigated using a single-sided boron-doped diamond (BDD) anode, its performance in TOC removal was similar to that of the Ti-Pt/β-PbO₂ anode; considering the higher oxidation power of BDD, the surprisingly good comparative performance of the Ti-Pt/β-PbO₂ anode was ascribed to significantly better hydrodynamic conditions attained in the filter-press reactor used with this electrode. Five initial oxidation intermediates were identified by LC-MS/MS and completely removed after 4 h of electrolysis; since they have also been determined in other degradation processes, there must be similarities in the involved oxidation mechanisms. Five terminal oxidation intermediates (acetic, formic, oxamic, propionic, and succinic acids) were identified by LC-UV and all of them (except acetic acid) were removed after 10 h of electrolysis.

Revegetation of the riparian zone of the Three Gorges Dam Reservoir leads to increased soil bacterial diversity

Abstract

As one of the most active components in soil, bacteria can affect soil physicochemical properties, its biological characteristics, and even its quality and health. We characterized dynamics of the soil bacterial diversity in planted (with Taxodium distichum) and unplanted soil in the riparian zone of the Three Gorges Dam Reservoir (TGDR), in southwestern China, in order to accurately quantify the changes in long-term soil bacterial community structure after revegetation. Measurements were taken annually in situ in the TGDR over the course of 5 years, from 2012 to 2016. Soil chemical properties and bacterial diversity were analyzed in both the planted and unplanted soil. After revegetation, the soil chemical properties in planted soil were significantly different than in unplanted soil. The effects of treatment, time, and the interaction of both time and treatment had significant impacts on most diversity indices. Specifically, the bacterial community diversity indices in planted soil were significantly higher and more stable than that in unplanted soil. The correlation analyses indicated that the diversity indices correlated with the pH value, organic matter, and soil available nutrients. After revegetation in the riparian zone of the TGDR, the soil quality and health is closely related to the observed bacterial diversity, and a higher bacterial diversity avails the maintenance of soil functionality. Thus, more reforestation should be carried out in the riparian zone of the TGDR, so as to effectively mitigate the negative ecological impacts of the dam. Vegetating the reservoir banks with Taxodium distichum proved successful, but planting mixed stands of native tree species could promote even higher riparian soil biodiversity and improved levels of ecosystem functioning within the TGDR.

Accumulation and distribution of PAHs in winter wheat from areas influenced by coal combustion in China

Abstract

In order to investigate level and potential sources of polycyclic aromatic hydrocarbons (PAHs) in wheat fields affected by coal combustion in Henan and Shaanxi Provinces and to investigate distribution and transfer of PAHs in winter wheat grown in the areas, various tissues of the crop and the corresponding rhizosphere soils were collected during the harvest season of winter wheat. The mean concentrations of USEPA 15 priority PAHs (sum of the three- to six-ring PAHs) ranged from 486 to 1117 μg kg⁻¹ in the rhizosphere soils, indicating serious PAH contamination. Based on both the isomeric ratios of PAHs and a principal component analysis (PCA), the main sources of PAHs in the agricultural soils were from combustion of biomass, coal and petroleum, and petroleum. ∑₁₅PAHs were significantly (p < 0.001) higher in the roots (287–432 μg kg⁻¹) than those in aerial tissues (221–310 μg kg⁻¹). There were two decreasing gradients of PAH concentrations, one from roots, stems to leaves, and the other from glumes to grains. Regardless of sampling sites, most PAHs detected in the roots and in the aerial tissues were three-ring PAHs (acenaphthene, acenaphthylene, fluorene, phenanthrene, and anthracene) and the percentages of three-ring PAHs were much higher in the aerial tissues (72.5–82.7%) than in the roots (49.5–74.0%) and in the rhizosphere soils (36.3–65.7%). The distribution of PAHs with different ring numbers in the stems, leaves, and glumes was quite similar to each other but was significantly different from that of the roots and rhizosphere soils. Combined with significant results from partial correlation and linear regression models, the present study suggested that partial three- to four-ring PAHs in the aerial tissues are derived from root-soil uptake and that six-ring PAHs may come from the air-to-leaf pathway, although the quantity contribution of foliar uptake and root uptake was yet to be further studied.

Disruption of ppr3, ppr4, ppr6, or ppr10 induces flocculation and filamentous growth in Schizosaccharomyces pombe

Abstract

Pentatricopeptide repeat (PPR) proteins are major players in mitochondrial and chloroplast RNA metabolism which is essential for normal organellar function. The fission yeast Schizosaccharomyces pombe has ten PPR proteins. We have previously reported that loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis leading to accumulation of reactive oxygen species and apoptotic cell death. In the present study, we show that loss of ppr3, ppr4, ppr6, or ppr10 can cause non-sexual flocculation and filamentous growth of cells. Furthermore, expression of a number of genes encoding cell-surface flocculins and cell wall-remodeling enzymes are induced in these ppr-deletion mutants. We also show that Δppr10 cells, and, to a lesser extent, Δppr4 and Δppr6 cells, exhibited increased tolerance to H₂O₂ toxicity compared with the wild-type strain. Finally, we found overexpression of genes involved in iron uptake and/or iron homeostasis could cause the flocculation of wild-type cells. Our findings suggest that elevated level of intracellular iron in the mutant caused by loss of ppr3, ppr4, ppr6, or ppr10 may result in flocculation and filamentous growth in S. pombe.

“Strongly Recommended” Revisiting Decisional Privacy to Judge Hypernudging in Self-Tracking Technologies

Abstract

This paper explores and rehabilitates the value of decisional privacy as a conceptual tool, complementary to informational privacy, for critiquing personalized choice architectures employed by self-tracking technologies. Self-tracking technologies are promoted and used as a means to self-improvement. Based on large aggregates of personal data and the data of other users, self-tracking technologies offer personalized feedback that nudges the user into behavioral change. The real-time personalization of choice architectures requires continuous surveillance and is a very powerful technology, recently coined as "hypernudging." While users celebrate the increased personalization of their coaching devices, "hypernudging" technologies raise concerns about manipulation. This paper addresses that intuition by claiming that decisional privacy is at stake. It thus counters the trend to solely focus on informational privacy when evaluating information and communication technologies. It proposes that decisional privacy and informational privacy are often part of a mutually reinforcing dynamic. Hypernudging is used as a key example to illustrate that the two dimensions should not be treated separately. Hypernudging self-tracking technologies compromise autonomy because they violate informational and decisional privacy. In order to effectively judge whether technologies that use hypernudges empower users, we need both privacy dimensions as conceptual tools.

Decreased ZnO nanoparticle phytotoxicity to maize by arbuscular mycorrhizal fungus and organic phosphorus

Abstract

ZnO nanoparticles (NPs) are applied in a wide variety of applications and frequently accumulate in the environment, thus posing risks to the environment and human health. Arbuscular mycorrhizal (AM) fungi (AMF) associate symbiotically with roots of most higher plants, helping their host plants acquire phosphorus (P). AMF can reduce the toxicity of ZnO NPs, but the benefits of AMF to host plants highly vary with soil available P. We hypothesize that organic P may help AMF to alleviate ZnO NP phytotoxicity. Here, we investigated the effects of inoculation with Funneliformis mosseae on plant growth and Zn accumulation, using maize grown in soil-sand mix substrates spiked with ZnO NPs (0 or 500 mg kg⁻¹) under different organic P supply levels (0, 20, or 50 mg kg⁻¹). The results showed addition of ZnO NPs inhibited root colonization rate, increased the shoot/root P concentration ratio, and led to significant Zn accumulation in soil and plants. As predicted, AM effects on maize plants all varied with P supply levels, both with or without ZnO NP additions. Organic P interacted synergistically with AMF to promote plant growth and acquisition of P, N, K, Fe, and Cu. AM inoculation reduced the bioavailable Zn released from ZnO NPs and decreased the concentrations and translocation of Zn to maize shoots. In conclusion, ZnO NPs caused excess Zn in soil and plants, posing potential environmental risks. However, our present results first demonstrate that organic P exhibited similar positive effects to AMF and interacted synergistically with AMF to improve plant growth and nutrition, and to decrease Zn accumulation and partitioning in plants, and thus helped diminish the adverse effects induced by ZnO NPs.

Septal Chondromucosal Grafts in Paralytic Lagophthalmos

Publication date: Available online 5 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Rouffet Alban, Florczak anne sophie, Vimont Thibault, Deranque clément, Boucher Sophie, Rousseau Pascal
ObjectiveThe risk of sight-threatening complications related to facial paralysis makes palpebral fissure management a priority. Surgery must take account of and adapt to the clinical signs of paralytic lagophthalmos. This therefore presupposes that a sufficient therapeutic arsenal is available. In this report, we propose a technique for palpebral lengthening (lower and/or upper), reconstructing the posterior lamella using a chondromucosal graft harvested from the nasal septum, combined with anterior lamellar repositioning.Patients and MethodA 5-year single center retrospective study was conducted, including sixteen patients for a total of nineteen septal chondromucosal grafts. The only inclusion criterion was paralytic lagophthalmos. Functional ophthalmic deficits were recorded (main outcome measure), first preoperatively, then postoperatively. Additionally, the degree of lagophthalmos was measured in order to infer palpebral fissure elongation gain. Surgical consequences and complications were recorded.ResultsA rapid regression in functional ophthalmic deficits was observed in 87% of patients, improving in stability over time (mean follow-up interval of 34 months). Mean palpebral fissure elongation gain was 3mm. 53% of patients suffered from complete occlusion of the palpebral fissure. Surgical consequences were uncomplicated. 38% of patients eventually underwent revision surgery.ConclusionPalpebral fissure lengthening using septal chondromucosal grafts serves as an alternative to existing treatment methods for paralytic lagophthalmos. Robust functional and cosmetic results, combined with very low morbidity, make this a simple and efficient technique whose indications may be extended.

Revealing Measles Outbreak Risk With a Nested IgG Serosurvey in Madagascar

Abstract

Madagascar reports few measles cases annually and high vaccination campaign coverage. However, the underlying age profile of immunity and risk of a measles outbreak is unknown. We conducted a nested serological survey, testing 1,005 serum collected between November 2013 and December 2015 via Madagascar's febrile rash surveillance system, for measles immunoglobulin G antibody titers. We directly estimated the age profile of immunity and compared these estimates to indirect estimates based on a birth cohort model of vaccination coverage and natural infection. Combining these estimates of the age profile of immunity in the population with an age-structured model of transmission, we further predicted the risk of a measles outbreak, and the impact of mitigation strategies designed around supplementary immunization activities. The direct and indirect estimates of age-specific seroprevalence show that current measles susceptibility is over 10%, and modeling suggests that Madagascar may be at risk of a major measles epidemic.

Heavy metals and arsenic content in water along the southern Caspian coasts in Iran

Abstract

Due to the importance of pollution monitoring in marine ecosystems and lack of a coherent and systematic investigation of heavy metal ions along the southern shores of the Caspian Sea, in the present study, the amount of these metals and As ions in coastal waters along its 780-km-long coast in Iran have been studied. Heavy metals (cobalt, nickel, copper, zinc, cadmium, mercury, lead) and a poisonous metalloid (arsenic) were selected in 59 sampling stations and determined using differential pulse polarography method. The multivariate statistical tools were applied to describe and interpret the experimental data. The overall mean concentrations of studied metals (in microgram per liter; μg L⁻¹) in the samples were found in the order Zn (10.9) > Ni (7.4) > Cu (5.5) > Pb (1.9) > Hg (1.4) > As (1.3) > Co (1.1) > Cd (0.2). The results when compared with reported international standards confirmed that the sampled waters do contain some of these elements above the suggested maximum permissible limits. Hg and Cu were detected in 54.2 and 72.9% of the samples, almost all above the permissible limits. Ni, Zn, Pb, and Co were detected in 100, 96.6, 93.2, and 88.1%, respectively, while 8.5, 22.0, 3.4, and 1.7% were above the permissible limits. Cd and As were present in 61 and 93% of the samples, and their concentrations were higher than the rate presented by Russian System of Management Chemicals (RSMC). In addition, spatial distribution of heavy metal concentrations showed that Gorgan Bay is an ecosystem serving as a filter, trapping natural and anthropogenic materials that are brought from industrial, commercial, and urbanized areas. The multivariate data analysis reveals that Caspian Sea is contaminated by both anthropogenic as well as pedo-geochemical sources.

nab-Paclitaxel Plus Carboplatin or Gemcitabine vs Gemcitabine Plus Carboplatin as First-Line Treatment for Patients With Triple-Negative Metastatic Breast Cancer: Results From the tnAcity Trial

Abstract

Background

Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and/safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC.

Patients and methods

Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1:1:1) nab-P 125 mg/m² plus C AUC 2, nab-P 125 mg/m² plus G 1000 mg/m², or G 1000 mg/m² plus C AUC 2, all on days 1, 8 q3w. Phase II primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety.

Results

In total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C vs nab-P/G (median, 8.3 vs 5.5 months; HR, 0.59 [95% CI, 0.38-0.92]; P = .02) or G/C (median, 8.3 vs 6.0 months; HR, 0.58 [95% CI, 0.37-0.90]; P = .02). OS was numerically longer with nab-P/C vs nab-P/G (median, 16.8 vs 12.1 months; HR, 0.73 [95% CI, 0.47-1.13]; P = .16) or G/C (median, 16.8 vs 12.6 months; HR, 0.80 [95% CI, 0.52-1.22]; P = .29). ORR was 73%, 39%, and 44% respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic.

Conclusions

First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile vs nab-P/G or G/C.

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

Abstract

Background

The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.

Material and methods

A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).

Results

Nine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.

Conclusion

In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.

PROSPERO registration number

CRD42018080042.