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Summary: Background: Specific trichoscopic signs of tinea capitis (TC) were first described in 2008. The accuracy of this diagnostic tool has not been evaluated. Objectives: To assess the diagnostic accuracy of trichoscopy. Methods: A prospective, multicentre study was done between March 2015 and March 2017 at the dermatology departments of four French university medical centres. Patients with a presumed diagnosis of TC were included. Trichoscopy was considered to be positive if at least one specific trichoscopic sign was observed. Trichoscopy results were compared with the gold standard for diagnosis of TC (mycological culture). Results: One hundred patients were included. Culture was positive for 53 patients and negative for 47. The sensitivity of trichoscopy was 94% [95% confidence interval (CI) 88–100], specificity was 83% (95% CI 72–94), positive predictive value was 92% and negative predictive value was 86%. Comma hairs, corkscrew hairs, zigzag hairs, Morse‐code‐like hairs and whitish sheath were significantly more frequent in patients with a positive mycological culture (P < 0·001). Comma hairs were more frequent in patients with Trichophyton TC (P = 0·026), and zigzag hairs were more frequent in patients with Microsporum TC (P < 0·001). Morse‐code‐like hair was not observed in any patients with Trichophyton TC and therefore appears to be highly specific for Microsporum TC. Conclusions: The presence of a single trichoscopic finding is predictive of TC. Trichoscopy is a useful, rapid, painless, highly sensitive tool for the diagnosis of TC – even for dermoscopists with little experience of trichoscopy. It enhances physicians' ability to make treatment decisions. What's already known about this topic? Tinea capitis (TC) must be confirmed by a mycological culture that may take up to 6 weeks, delaying treatment.Specific trichoscopic signs of TC were first described in 2008, but the accuracy of trichoscopy for diagnosing TC has not previously been evaluated. What does this study add? The present series is the largest yet on the use of trichoscopy in the diagnosis of TC.Our results demonstrated that the presence of a single feature (comma hair, corkscrew hair, zigzag hair, Morse‐code‐like hair or whitish sheath) is predictive of TC.Trichoscopy is painless and highly sensitive.Morse‐code‐like hair appears to be highly specific for Microsporum TC. Linked Comment: Brasileiro. Br J Dermatol 2019; 181:893–894. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

The threshold displacement energy in iron is determined usingab initiomolecular dynamics. This is the most fundamental input parameter for radiation damage assessments. The predictions agree well with the available experiments and provide a significantly lower average value for iron than the standard one. This result impacts radiation damage assessments in iron alloys and steels and especially so for dose estimations and conditions close to the threshold. The importance of using an appropriate description of the core and valence electrons is highlighted. Energy loss simulations provide important fitting parameters for improved interatomic potentials. IMPACT STATEMENTGround-breakingab initiocalculations of the threshold displacement energies in iron show significant differences in the angular anisotropy and predicted average value with respect to previous literature. [ABSTRACT FROM PUBLISHER]

Post-irradiation annealing experiments are often used to obtain clearer information on the nature of defects produced by irradiation. However, their interpretation is not always straightforward without the support of physical models. We apply here a physically-based set of parameters for object kinetic Monte Carlo (OKMC) simulations of the nanostructural evolution of FeMnNi alloys under irradiation to the simulation of their post-irradiation isochronal annealing, from 290 to 600 °C. The model adopts a 'grey alloy' scheme, i.e. the solute atoms are not introduced explicitly, only their effect on the properties of point-defect clusters is. Namely, it is assumed that both vacancy and SIA clusters are significantly slowed down by the solutes. The slowing down increases with size until the clusters become immobile. Specifically, the slowing down of SIA clusters by Mn and Ni can be justified in terms of the interaction between these atoms and crowdions in Fe. The results of the model compare quantitatively well with post-irradiation isochronal annealing experimental data, providing clear insight into the mechanisms that determine the disappearance or re-arrangement of defects as functions of annealing time and temperature. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman. [ABSTRACT FROM AUTHOR]

Predicting the behaviour of a component under irradiation or submitted to an external load often requires understanding the evolution of its microstructure. This usually requires knowledge of the mechanisms taking place at the atomic level, which are introduced in multiscale-type modelling suites. In this context, interatomic potentials are necessary ingredients for most simulation techniques at the atomic level. They have been used for more than 40 years in various areas of materials science and, in particular, in the fields of radiation damage and plasticity. These simulations have shed particular light on the role of solute atoms in the formation of the primary damage or the motion of dislocations. However, ab initio calculations, as well as comparison of the results obtained with different interatomic potentials have indicated some failures in these potentials, which led to the building of new potentials. This article highlights how ab initio calculations, which nowadays constitute the state of the art method to predict atomic properties can (and will) increasingly contribute to the assessment, validation and building of interatomic potentials. [ABSTRACT FROM AUTHOR]

Summary: 这项研究是在法国的四所大学医院进行,旨在评估该技术(毛发镜检)在诊断头癣,也称为头皮癣方面的有用性。 头癣是真菌感染头皮毛发和周围皮肤的一种疾病。真菌是可以生活在头发、指甲和皮肤表层的显微镜下微生物。它在儿童中常见,主要治疗方法是口服抗真菌药。 目前,头癣可通过头发培养(采集样本并在实验室中生长真菌)或遗传分析诊断。 毛发镜检是使用称为皮肤镜的手持式放大镜进行显微镜检查的一种形式,使用放大镜可以让受过培训的人员看到头发生长和形状的细微差别。 本研究是由皮肤病学实习生与一位专家评估人员一起进行的,他们还对患者进行了检查。结果发现,毛发镜检显示受感染头发中有许多可见的变化,且各自可根据特定的可识别特征来命名,例如,开瓶器头发或莫尔斯电码头发。发现这些变化中仅有一种是感染的准确预测指标,后续得到实验室证实。 这些结果表明,这种简单的观察技术可用于准确诊断头癣。此外,一些可见的变化是特定真菌所特有的。这有助于皮肤科医生选择正确的抗真菌药物治疗方法,这些治疗方法对于不同微生物而言各不相同。 Linked Article: Dhaille et al. Br J Dermatol 2019; 181:1046–1051 [ABSTRACT FROM AUTHOR]

Summary: This study which was carried out in four university hospitals in France was designed to assess the usefulness of the technique, trichoscopy, in the diagnosis of tinea capitis, also known as scalp ringworm. Tinea capitis is an infection of the scalp hair and the surrounding skin with a fungus. Fungi are microscopic organisms that can live on the hair, nails, and outer skin layer. It is common in children and the main treatment is a course of antifungal drugs taken by mouth. Currently tinea capitis is diagnosed by culture (taking samples and growing the fungi in a lab) or genetic analysis of the hair. Trichoscopy is a form of microscopic examination using a hand‐held magnifier called a dermatoscope, which allows someone trained in its use to see minute differences in the growth and shape of hairs. The study was carried out by dermatology trainees with an expert assessor who also examined the patients. The results found that trichoscopy showed a number of visible changes in infected hairs, each named for a specific identifiable feature e.g. corkscrew hairs or morse code hairs. The presence of just one of these changes was found to be an accurate predictor of infection, which was subsequently confirmed by the laboratory. These results suggest that this simple observational technique can be used to diagnose tinea capitis with accuracy. Furthermore, some of the visible changes are specific to particular fungi. This helps the dermatologist in selecting the correct treatment with antifungal medicines, which is different for different organisms. Linked Article: Dhaille et al. Br J Dermatol 2019; 181:1046–1051 [ABSTRACT FROM AUTHOR]

The first step towards the understanding and the modelling of the Fe-Cr alloy kinetic properties consists in estimating the migration energies related to the processes that drive the microstructure evolution. The vacancy's migration barrier is expected to depend on the vacancy-migrating atom pair atomic environment as pointed out by Nguyen-Manh et al. or Bonny et al. In this paper, we address the issue of the dependence on the vacancy's local atomic environment of both the vacancy migration energy and the configurational energy change ΔE that occurs when the vacancy jumps towards one of its nearest neighbour sites. A DFT approach is used to determine the ground state energy associated to a given configuration of the system. The results are interpreted in the light of the chromium-chromium and chromium-vacancy binding energies as well as the substitutional chromium atoms magnetic properties. [ABSTRACT FROM AUTHOR]

The influence of the local environment on vacancy and self-interstitial formation energies has been investigated in a face-centered-cubic (fcc) Fe-10Ni-20Cr model alloy by analyzing an extensive set of first-principle calculations based on density functional theory. Chemical disorder has been considered by designing special quasirandom structures and four different collinear magnetic structures have been investigated in order to determine a relevant reference state to perform point defect calculations at 0 K. Two different convergence methods have also been used to characterize the importance of the method on the results. Although our fcc Fe-10Ni-20Cr would be better represented in terms of applications by the paramagnetic state, we found that the antiferromagnetic single-layer magnetic structure was the most stable at 0 K and we chose it as a reference state to determine the point defect properties. Point defects have been introduced in this reference state, i.e., vacancies and Fe-Fe, Fe-Ni, Fe-Cr, Cr-Cr, Ni-Ni, and Ni-Cr dumbbell interstitials oriented either parallel or perpendicular to the single layer antiferromagnetic planes. Each point defect studied was introduced at different lattice sites to consider a sufficient variety of local environments and analyze its influence on the formation energy values. We have estimated the point defect formation energies with linear regressions using variables which describe the local environment surrounding the point defects. The number and the position of Ni and Cr first nearest neighbors to the point defects were found to drive the evolution of the formation energies. In particular, Ni is found to decrease and Cr to increase the vacancy formation energy of the model alloy, while the opposite trends are found for the dumbbell interstitials. This study suggested that, to a first approximation, the first nearest atoms to point defects can provide reliable estimates of point defect formation energies. [ABSTRACT FROM AUTHOR]

Extensive efforts have been dedicated to developing cell-specific targeting ligands that can be conjugated to therapeutic cargo, offering a promising yet still challenging strategy to deliver oligonucleotide therapeutics beyond the liver. Indeed, while the cargo and the ligand are crucial, the third component, the linker, is integral but is often overlooked. Here, we present strain-promoted sydnone-alkyne cycloaddition as a versatile linker chemistry for oligonucleotide synthesis, expanding the choices for bioconjugation of therapeutics while enabling subcellular detection of the linker and payload using nanoscale secondary ion mass spectrometry (NanoSIMS) imaging. This strategy was successfully applied to peptide and lipid ligands and profiled using the well characterized N -acetylgalactosamine (GalNAc) targeting ligand. The linker did not affect the expected activity of the conjugate and was detectable and distinguishable from the labeled cargo. Finally, this work not only offers a practical bioconjugation method but also enables the assessment of the linker's subcellular behavior, facilitating NanoSIMS imaging to monitor the three key components of therapeutic conjugates.

Aims: To describe the demographic characteristics of heroin and cocaine injectors with chronic injection-related trophic disorders, as well as the clinical and progressive characteristics of these disorders., Methods: A descriptive, observational, multicenter and retrospective study over the last 15 years. Patients were recruited via a call for cases and by consulting the health data warehouse of the university hospital center., Results: The population comprised 39 injection drug users, of whom 79.5% were male, with a median age of 41 years. Subjects had numerous co-addictions and 70.5% were infected with hepatitis C virus. Trophic disorders were multiple in some cases: 43.5% of patients had lymphoedema, 87% had ulcers, and 56.5% had injection-related scars. Ulcers were multiple, large, and present for a median of 3 years. They were located on the upper limbs in 32.5% of cases. Ulcers constituted a source of complications in 64.5% of cases and these were infectious in 91% of cases (local, osteoarticular or systemic). During follow-up, 8 patients died and 21.5% of patients requiring ulcer care were lost to follow-up., Conclusions: This study showed a high rate of complications, particularly infections, of ulcers in injection drug users. Localization of these ulcers to the upper limbs, although rare in the general population, is relatively frequent in this population. Follow-up is difficult and cooperation between dermatologist and addictologist is essential to improve patient care., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Olivier Cottencin has acted as a chairman or speaker of symposia organized by Janssen, Indivior, and Recordati.]., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Increased saturated fatty acid (SFA) levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased SFA content in cell membranes negatively impacts adipocyte insulin signaling. Preadipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking twofold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes. Similar changes in phospholipid composition were observed in white adipose tissues isolated from the ADIPOR2-knockout mice. The SFA levels in phospholipids could be further increased by treating ADIPOR2-deficient cells with palmitic acid and resulted in reduced membrane fluidity and endoplasmic reticulum stress in mouse and human preadipocytes. Strikingly, increased SFA levels in differentiated adipocyte phospholipids had no effect on adipocyte gene expression or insulin signaling in vitro. Similarly, increased adipocyte phospholipid saturation did not impair white adipose tissue function in vivo, even in mice fed a high-saturated fat diet at thermoneutrality. We conclude that increasing SFA levels in adipocyte phospholipids is well tolerated and does not affect adipocyte insulin signaling in vitro and in vivo., (© 2023 by the American Diabetes Association.)

Background: Systemic treatment options for psoriasis are limited for patients with recent neoplasia., Objectives: We report the real-life use of apremilast (APR) in patients with psoriasis and recent cancer., Materials & Methods: We conducted a retrospective, multicentre study in five hospitals and among 120 private dermatologists in the north of France from January 2015 to May 2021. We included patients treated with APR for psoriasis and suffering from an active cancer or who had been diagnosed with a cancer or treated for a cancer within the last five years., Results: We included 23 patients diagnosed with a cancer, on average 2.6 years before the introduction of APR for psoriasis. In most patients, APR was specifically chosen due to oncological history. At 16±8 weeks, 55% (n=11/20) of patients had achieved PASI 50 score, 30% (n=6/20) PASI 75, 5% (n=3/20) PASI 90 and 37.5% (n=3/8) of them had a significant improvement in quality of life. Non-serious adverse events were observed in 65.2% (n=15/23) of patients (diarrhoea in 39%), resulting in discontinuation of treatment for 27.8%. The average duration of treatment was 303.8±252.4 days. For four patients, a recurrence or a progression of cancer was recorded during APR treatment., Conclusion: In our patients with both psoriasis and cancer, APR improved quality of life, with a good safety profile. A larger study, matched for type, stage and treatment of underlying cancer, would be necessary to draw further conclusions about the oncological safety of APR.

Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity. Here, we used a combination of electron microscopy and NanoSIMS to assess the subcellular concentrations of a 34 S-labeled GalNAc-ASO and a naked ASO in the organelles of primary human hepatocytes. We first cross-validated the method by including a 127 I-labeled ASO, finding that the absolute concentration of the lysosomal ASO using two independent labeling strategies gave matching results, demonstrating the strength of our approach. This work also describes the preparation of external standards for absolute quantification by NanoSIMS. For both the 34 S and 127 I approaches used for our quantification methodology, we established the limit of detection (5 and 2 μM, respectively) and the lower limit of quantification (14 and 5 μM, respectively).

The delivery of antisense oligonucleotides (ASOs) to specific cell types via targeted endocytosis is challenging due to the low cell surface expression of target receptors and inefficient escape of ASOs from the endosomal pathway. Conjugating ASOs to glucagon-like peptide 1 (GLP1) leads to efficient target knockdown, specifically in pancreatic β-cells. It is presumed that ASOs dissociate from GLP1 intracellularly to enable an ASO interaction with its target RNA. It is unknown where or when this happens following GLP1-ASO binding to GLP1R and endocytosis. Here, we use correlative nanoscale secondary ion mass spectroscopy (NanoSIMS) and transmission electron microscopy to explore GLP1-ASO subcellular trafficking in GLP1R overexpressing HEK293 cells. We isotopically label both eGLP1 and ASO, which do not affect the eGLP1-ASO conjugate function. We found that the eGLP1 peptide and ASO are not detected at the same level in the same endosomes, within 30 min of GLP1R-HEK293 cell exposure to eGLP1-ASO. When we utilized different linker chemistry to stabilize the GLP1-ASO conjugate, we observed more ASO located with GLP1 compared to cell incubation with the less stable conjugate. Overall, our work suggests that the ASO separates from GLP1 relatively early in the endocytic pathway, and that linker chemistry might impact the GLP1-ASO function.

Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction. We have previously shown that epidermis-specific A20 knockout mice (A20 EKO ) develop mild epidermal hyperplasia but no macroscopic skin inflammation. We now show that various cytokines and chemokines are up-regulated in A20 EKO mouse skin. A20 EKO mice also display systemic proinflammatory changes, even in the absence of skin immune cell infiltration, and an exacerbated disease severity upon induction of experimental psoriasis, atopic dermatitis, or skin barrier disruption. Keratinocytes showed increased proinflammatory gene expression in the absence of A20 in unstimulated and IL-17A-stimulated conditions, in part resulting from uncontrolled MyD88-dependent signaling. Our findings indicate that absence of A20 in keratinocytes leads to systemic inflammation at homeostatic conditions and is sufficient to exacerbate inflammatory skin disorders associated with different immune profiles by increasing cytokine and chemokine expression., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)