Skin hyperpigmentation after sclerotherapy with polidocanol: A systematic review.

Skin hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants is a common local side effect. Sclerotherapists should be familiar with factors that trigger hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants. A systematic literature review of works reporting hyperpigmentation after sclerotherapy for telangiectasias, reticular veins, side branches and truncal varices with polidocanol-containing sclerosants was performed. Reported incidence rates, follow-up periods and potentially triggering factors were assessed and analysed. The search yielded 1687 results; of these, 27 reports met the inclusion criteria. The incidence of hyperpigmentation seemed to increase with higher concentrations of polidocanol and was more evident after sclerotherapy for epifascial veins than for intrafascial truncal veins when the polidocanol concentration was more than 0.25%. Regarding sclerotherapy for telangiectasias and reticular veins, the incidence of hyperpigmentation ranged between 2% and 25% for polidocanol 0.25% (liquid and foam), between 12.5% and 67.9% for polidocanol 0.5% (liquid and foam) and between 13% and 73% for polidocanol 1% (liquid and foam). Regarding truncal veins, the incidence ranged from 7% to 45.8% for polidocanol 1% (liquid and foam), from 16% to 17% for polidocanol 2% (foam) and from 7.4% to 32.5% for polidocanol 3% (liquid and foam). Regarding the treatment of side branches, the incidence of hyperpigmentation ranged from 5.6% to 53% for both foam and liquid sclerotherapy. Regarding the duration of hyperpigmentation, there are few data describing reticular veins and telangiectasias. Hyperpigmentation persisting for more than 6 months has been reported to have an incidence of up to 7.5%. Hyperpigmentation persisting for more than 1 year after foam polidocanol 1%-3% treatment for truncal veins has an incidence ranging from 8.1% to 17.5%. Other factors such as higher volumes and compression therapy after treatment seem to have a minor influence. Data regarding hyperpigmentation after polidocanol-related sclerotherapy are poor and should be improved by higher-quality research.

Reinventing European air traffic control based on the covid-19 pandemic experience.

This article/paper proposes to take advantage of the crisis resulting from COVID-19 and its' impact on Air Traffic Control (ATC) in Europe to reinvent it. The article explains its evolution, in particular, 20 years of Single European Sky reform process not having overcome the gridlock. The impact of the COVID-19 on aviation in general and specifically on ATC is described. It focuses on the avenues to overcome fragmentation and competing interests of the various stakeholders by reinventing EUROCONTROL Organisation as the agent to recover from the economic crisis.

Reliability Assessment and Validation of the Skin Hyperpigmentation Index Compared to the Physician Global Assessment Score.

BACKGROUND: The skin hyperpigmentation index (SHI), a new objective method for measuring skin hyperpigmentation, needs validation. OBJECTIVE: To gain evidence of the reliability and validity of the SHI. METHODS: Fifteen raters were divided into 3 groups (5 dermatologists, 5 nondermatologist physicians, and 5 nonphysician clinicians). Each rated 5 pigmented mole lesions with mild-to-severe hyperpigmentation to determine intra- and interrater reliability. All raters photographed the lesions and rated them using the subjective Physician Global Assessment (PGA) score. The same photographs were then assessed based on automatic computer measurement software using the online SHI tool (https://shi.skinimageanalysis.com). RESULTS: The SHI reliability was excellent for all intra- and interrater assessments, while most PGA assessments showed good intra- and interrater agreement. Between-group reliability was excellent for SHI, while moderate-to-good for PGA evaluations. Concordance between the SHI and PGA assessments was strong across all groups of assessors. CONCLUSION: There is evidence that the SHI is a reliable instrument for measuring skin hyperpigmentation, and can be used by nonexperienced clinicians.

Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex.

The yeast THO complex is recruited to active genes and interacts with the RNA-dependent ATPase Sub2 to facilitate the formation of mature export-competent messenger ribonucleoprotein particles and to prevent the co-transcriptional formation of RNA:DNA-hybrid-containing structures. How THO-containing complexes function at the mechanistic level is unclear. Here, we elucidated a 3.4 Å resolution structure of Saccharomyces cerevisiae THO-Sub2 by cryo-electron microscopy. THO subunits Tho2 and Hpr1 intertwine to form a platform that is bound by Mft1, Thp2, and Tex1. The resulting complex homodimerizes in an asymmetric fashion, with a Sub2 molecule attached to each protomer. The homodimerization interfaces serve as a fulcrum for a seesaw-like movement concomitant with conformational changes of the Sub2 ATPase. The overall structural architecture and topology suggest the molecular mechanisms of nucleic acid remodeling during mRNA biogenesis.

Prognostic markers in lentigo maligna patients treated with imiquimod cream: A long-term follow-up study.

BACKGROUND: More data are needed to define factors that predict long-term success after imiquimod therapy for lentigo maligna (LM). OBJECTIVE: We sought to determine the demographic, clinical, and histologic prognostic markers of relapse-free survival in patients with LM who were treated with imiquimod. METHODS: This was a single-arm, open-label, nonrandomized, prospective study. RESULTS: Eighty-nine patients with histologically confirmed LM and a median follow-up time of 4.8 years after imiquimod treatment were included in our study. Sixteen patients (18%) relapsed. Statistically significant indicators of an increased risk of local recurrence included: the total number of melanocytes, the number of basal and suprabasal melanocytes and the number of pagetoid spreading melanocytes. LIMITATIONS: Our study was a single-center, nonrandomized study. CONCLUSION: An assessment of different melanocyte fractions in the diagnostic baseline biopsy specimen may help to predict the response of LM to imiquimod therapy.

RNA degradation paths in a 12-subunit nuclear exosome complex.

The eukaryotic exosome is a conserved RNA-degrading complex that functions in RNA surveillance, turnover and processing. How the same machinery can either completely degrade or precisely trim RNA substrates has long remained unexplained. Here we report the crystal structures of a yeast nuclear exosome containing the 9-subunit core, the 3'-5' RNases Rrp44 and Rrp6, and the obligate Rrp6-binding partner Rrp47 in complex with different RNAs. The combined structural and biochemical data of this 12-subunit complex reveal how a single-stranded RNA can reach the Rrp44 or Rrp6 active sites directly or can bind Rrp6 and be threaded via the central channel towards the distal RNase Rrp44. When a bulky RNA is stalled at the entrance of the channel, Rrp6-Rrp47 swings open. The results suggest how the same molecular machine can coordinate processive degradation and partial trimming in an RNA-dependent manner by a concerted swinging mechanism of the two RNase subunits.

Structural model of a CRISPR RNA-silencing complex reveals the RNA-target cleavage activity in Cmr4.

The Cmr complex is an RNA-guided endonuclease that cleaves foreign RNA targets as part of the CRISPR prokaryotic defense system. We investigated the molecular architecture of the P. furiosus Cmr complex using an integrative structural biology approach. We determined crystal structures of P. furiosus Cmr1, Cmr2, Cmr4, and Cmr6 and combined them with known structural information to interpret the cryo-EM map of the complex. To support structure determination, we obtained residue-specific interaction data using protein crosslinking and mass spectrometry. The resulting pseudoatomic model reveals how the superhelical backbone of the complex is defined by the polymerizing principles of Cmr4 and Cmr5 and how it is capped at the extremities by proteins of similar folds. The inner surface of the superhelix exposes conserved residues of Cmr4 that we show are required for target-cleavage activity. The structural and biochemical data thus identify Cmr4 as the conserved endoribonuclease of the Cmr complex.

Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex.

The exosome is the major 3'-5' RNA-degradation complex in eukaryotes. The ubiquitous core of the yeast exosome (Exo-10) is formed by nine catalytically inert subunits (Exo-9) and a single active RNase, Rrp44. In the nucleus, the Exo-10 core recruits another nuclease, Rrp6. Here we crystallized an approximately 440-kilodalton complex of Saccharomyces cerevisiae Exo-10 bound to a carboxy-terminal region of Rrp6 and to an RNA duplex with a 3'-overhang of 31 ribonucleotides. The 2.8 Å resolution structure shows how RNA is funnelled into the Exo-9 channel in a single-stranded conformation by an unwinding pore. Rrp44 adopts a closed conformation and captures the RNA 3'-end that exits from the side of Exo-9. Exo-9 subunits bind RNA with sequence-unspecific interactions reminiscent of archaeal exosomes. The substrate binding and channelling mechanisms of 3'-5' RNA degradation complexes are conserved in all kingdoms of life.

[Local treatment of chronic skin wounds in a Swiss out-patient wound centre 2010]. / Lokale Behandlung von chronischen Hautwunden an einer Schweizerischen Wundambulanz 2010.

In Switzerland around 30,000 patients suffer from chronic skin wounds. Appropriate topical wound care along with treatment of the causes of the wounds enables to heal a lot of these patients and to avoid secondary disease such as infections. Thereby, the final goal of wound care is stable reepithelisation. Based on experience with chronic leg ulcers mainly in our out-patient wound centre, we give a survey of the wound dressings we actually use and discuss their wound-phase adapted application. Furthermore, we address the two tissue engineering products reimbursed in Switzerland, Apligraf and EpiDex, as well as the biological matrix product Oasis. The crucial question, which treatment options will be offered in future to the wound patients by our health regulatory and insurance systems, is open to debate.