EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Secondary solution for breast reconstruction following total DIEP flap loss: A single-center experience after 3270 DIEP flaps.

BACKGROUND: Total deep inferior epigastric perforator (DIEP) flap failure is a significant concern in autologous breast reconstruction. Literature on secondary reconstruction options following total flap failure is limited. This study outlines the outcomes of patients who underwent reconstruction post-DIEP flap failure at our institution. METHODS: We conducted a retrospective analysis of patients receiving autologous breast reconstruction between 2004 and 2021. We aimed to identify causes of total DIEP flap failure, outcomes of revision surgery, and outcomes of secondary breast reconstruction procedures. RESULTS: From 2004 to 2021, 3456 free flaps for breast reconstruction were performed, with 3270 being DIEP flaps for 2756 patients. DIEP flap failure was observed in 40 cases (1.22%). Bilateral reconstructions had a higher failure rate (2.31%) than unilateral (0.72%). The primary cause was intraoperative complications during flap harvest (18 cases), followed by insufficient arterial perfusion (seven cases). Other causes included postoperative hematoma (seven cases), venous congestion (six cases), and late-onset fat necrosis (two cases). Post-failure, five patients received a second free flap with three cases of repeated flap failure. Twenty patients received implant-based reconstruction with two cases of reconstruction failure, while seven patients received a pedicled latissimus dorsi (LD) flap reconstructions with no cases of reconstruction failure. Eight patients declined further reconstruction. CONCLUSION: A second free flap post-DIEP failure was associated with a high risk of reconstruction failure, suggesting the need for careful patient selection. Implant-based and pedicled LD flap seem to be reliable secondary reconstruction options.

Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.

Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.

Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.

We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.

Estrogen-related receptor gamma regulates mitochondrial and synaptic genes and modulates vulnerability to synucleinopathy.

Many studies implicate mitochondrial dysfunction as a key contributor to cell loss in Parkinson disease (PD). Previous analyses of dopaminergic (DAergic) neurons from patients with Lewy-body pathology revealed a deficiency in nuclear-encoded genes for mitochondrial respiration, many of which are targets for the transcription factor estrogen-related receptor gamma (Esrrg/ERRγ). We demonstrate that deletion of ERRγ from DAergic neurons in adult mice was sufficient to cause a levodopa-responsive PD-like phenotype with reductions in mitochondrial gene expression and number, that partial deficiency of ERRγ hastens synuclein-mediated toxicity, and that ERRγ overexpression reduces inclusion load and delays synuclein-mediated cell loss. While ERRγ deletion did not fully recapitulate the transcriptional alterations observed in postmortem tissue, it caused reductions in genes involved in synaptic and mitochondrial function and autophagy. Altogether, these experiments suggest that ERRγ-deficient mice could provide a model for understanding the regulation of transcription in DAergic neurons and that amplifying ERRγ-mediated transcriptional programs should be considered as a strategy to promote DAergic maintenance in PD.

Spacecraft sample collection and subsurface excavation of asteroid (101955) Bennu.

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon.

To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae. With the recent availability of high-quality genome sequences for 13 representative species and one relative (Xylaria hypoxylon) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa, products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.

[Definition of the quality of hand surgery]. / Definition von Qualität in der Handchirurgie.

The quality of treatment within the total concept of the healthcare system is subject to multifactorial influences. With the intention to improve the quality of hand surgery the German Society for Hand Surgery (DGH) has initiated a number of projects. These include the S3 guidelines codeveloped by the DGH, the hand trauma register of the DGH, the definition of criteria for hand surgical procedures to be performed in an outpatient setting within the framework of a consensus recommendation as well as participation in a large epidemiological study with the special documentation of pathological alterations of the hand to determine the prevalences (study of health in Pomerania, SHIP); however, within these projects the quality of treatment itself is not assessed. In the attempt to document the quality, the currently available quality indicators in hand surgery probably only evaluate the aspects really relevant for the patients to a limited extent. Therefore, the DGH participated at an early stage in the development of assessments within the international study named by the WHO as a lighthouse project. These developed and validated assessments are intended to include all aspects of the results including the individual patient view in order to precisely relate the quality of treatment to an exactly defined pattern of hand injury. The use of these assessments should permanently enable a prediction of outcome quality for each individual patient. All these projects require the largest involvement possible to collect as much data as possible. With this intention the DGH further coordinates and develops these projects within the committees of the extended executive board and attempts to motivate as many surgeons as possible to participate.

Double-Unit Superomedio-Central (DUS) Pedicle Inverted-T Reduction Mammaplasty in Gigantomastia: A 7-year Single-Center Retrospective Study.

INTRODUCTION: Reduction mammaplasty in patients with gigantomastia is challenging. The Double-Unit technique with a Superomedio-Central pedicle and inverted-T incision is the standard technique for reduction mammaplasty in our clinic. The aim of this study was to review our approach in cases with gigantomastia in comparison with the current literature. PATIENTS AND METHODS: From 01/2011 to 12/2017, we performed 831 reduction mammaplasties in 630 patients. The Double-Unit  Superomedio-Central  (DUS) pedicle and inverted-T incision was implemented as a standard procedure for gigantomastia. Patient demographics and the outcome parameters complication rate, patient satisfaction with the aesthetic result, nipple sensibility, and surgical revision rate were obtained and retrospectively analyzed. RESULTS: In 37 patients, 55 reduction mammaplasties were performed with more than 1000 g per breast. Mean resection weight was 1311 g on right side and 1289 g on left side. Mean age was 52.5 years, mean body mass index was 32.8 kg/m2, mean sternal-notch-to-nipple distance was 38.3 cm. A free NAC graft was necessary in four breasts. Overall complication rate was 14.5%; secondary surgical revision rate was 12.7%. 91% of the patients were "very satisfied" and "satisfied" with the aesthetic result. Nipple sensibility was rated "high" and "medium" in 83%. CONCLUSION: The Double-Unit technique with a Superomedio-Central pedicle and inverted-T incision is very effective to achieve volume reduction and aesthetically pleasing reproducible results with a low complication rate in cases with gigantomastia. LEVEL OF EVIDENCE: Level of Evidence This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Measurement of the Fluctuations in the Number of Muons in Extensive Air Showers with the Pierre Auger Observatory.

We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.

Characterization of staphylococci sampled from diabetic foot ulcer of Jordanian patients.

AIMS: The aim of this study was to isolate and characterize staphylococcal isolates from diabetic foot ulcers (DFU) in Jordanian patients. METHODS AND RESULTS: Selected aerobic pathogens recovered from DFU specimens and patients' nares with a focus on staphylococci were investigated. Antimicrobial susceptibilities and the prevalence of methicillin-resistant staphylococci (MRS) were determined. SCCmec types and toxigenic characteristics were analysed and spa typing was performed for methicillin-resistant Staphylococcus aureus (MRSA) isolates. The relationship between toxigenic characteristics of MRSA and the Wagner ulcer grading system was statistically analysed. A total number of 87 DFU patients were recruited for the study. The DFU cultures were polymicrobial. Members of the genus Staphylococcus were the most common among DFU-associated isolates found in 48·3% (n = 42) of all patients enrolled. Coagulase-negative staphylococci (CoNS) comprised 63·3% of staphylococci isolated from DFUs predominated by Staphylococcus epidermidis in both DFU (7·6%) and nares (39·2%). Staphylococcus aureus was isolated from DFUs and nares in 14·2 and 9·8%, respectively, while 93 and 70% of these isolates were MRSA. Most of MRSA carried SCCmec type IV (76·2%) while SCCmec elements were non-typeable in most methicillin resistant coagulase negative staphylococci (MR-CoNS) (61·9%). The most frequent MRSA spa type was t386 (23·8%). Most MRSA and MR-CoNS exhibited resistance towards aminoglycosides, fluoroquinolones and macrolides and susceptibility towards vancomycin, mupirocin and linezolid. No association was found between the possession of pvl, tst, sea and hlg toxins and Wagner ulcer grading system (P value >0·05). CONCLUSIONS: This analysis of Jordanian DFU culture demonstrated its polymicrobial nature with predominance of Staphylococcus sp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first of its type to assess the microbiology of DFU among Jordanian patients. The results will help in the appropriate application of antimicrobial chemotherapy in the management of DFU.

[Results of preoperative SARS-CoV-2 testing in the coronavirus pandemic]. / Ergebnisse der präoperativen SARS-CoV-2-Testung ("severe acute respiratory syndrome coronavirus 2") in der Coronaviruspandemie.

BACKGROUND: Surgery is challenging during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in elective and emergency surgery and to calculate the patient contacts during hospital stay. MATERIALS AND METHODS: All surgeries defined by the German procedural classification (starting with a 5) from 1 June until 29 November 2020 were retrospectively evaluated regarding the preoperative SARS-CoV­2 nasopharyngeal swab test. The results were then divided in emergency and elective surgeries. To show the personal contacts of the patients in a university hospital, we calculated the patient pathway within the department of urology and urosurgery for April 2020. Therefor we used the electronic patient records. RESULTS: Altogether 7745 surgical procedures in 5985 patients were performed, whereby 39 (0.5%) SARS-CoV­2 tests were positive. 2833 (37%) surgical procedures were emergency cases and 4912 (63%) were elective procedures. 25 (0.9%) of the emergency group and 14 (0.3%) of the elective surgeries had a positive SARS-CoV­2 test. The average number of contacts in the patient room was 12.83 (0-50) and 84.22 (0-249) at the ward level, not counting contacts with the clinic staff. CONCLUSIONS: Nearly 1% of the preoperative SARS-CoV­2 tests of either emergency or elective surgeries tested positive in the 6 months prior to November 2020. Although the risk of undetected SARS-CoV­2 infection appears to be low in terms of costs and personnel, preoperative screening is useful in high-risk areas to ensure further necessary surgeries, especially concerning cancer patients and to prevent virus spread in a hospital.

Extensively-drug-resistant Klebsiella pneumoniae ST307 outbreak strain from north-eastern Germany does not show increased tolerance to quaternary ammonium compounds and chlorhexidine.

BACKGROUND: An outbreak of extensively-drug-resistant Klebsiella pneumoniae strain ST307 in a cluster of hospitals in north-east Germany gave rise to the assumption that the epidemiological success of the strain could be based on increased tolerance to biocides. METHODS: The tolerance of the outbreak strain was compared with epidemiologically unrelated clinical isolates of K. pneumoniae, and reference strains of Pseudomonas aeruginosa (ATCC 15442) and Escherichia coli K12 (NCTC 10538). Tests were performed in a miniaturized assay based on European Standard EN 1040. The widely used biocides benzalkonium chloride (BAC) and didecyl dimethyl ammonium chloride (DDAC), their commercial formulation Descosept spezial (DS), and the antiseptic agent chlorhexidine digluconate (CHG) were selected as test substances. These biocides are used regularly in the hospitals involved in the outbreak. FINDINGS: All biocides had a bactericidal effect against all tested strains in the quantitative suspension test within 5 min at typically used concentrations and dilutions. The effectiveness of BAC and DDAC alone and in combination, and CHG antisepsis were not impaired under tested conditions. CONCLUSION: The outbreak strain did not show significantly increased tolerance towards biocides regarding the antiseptic. Thus, the epidemiological success of the strain has to be ascribed to other causes, such as inadequate hand hygiene of visitors.

Variations in color and reflectance on the surface of asteroid (101955) Bennu.

Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. Here we present multispectral images (0.44 to 0.89 micrometers) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials does not simply progress from red to blue (or vice versa). Instead, freshly exposed, redder surfaces initially brighten in the near-ultraviolet region (i.e., become bluer at shorter wavelengths), then brighten in the visible to near-infrared region, leading to Bennu's moderately blue average color. Craters indicate that the time scale of these color changes is ~105 years. We attribute the reflectance and color variation to a combination of primordial heterogeneity and varying exposure ages.

eV-Scale Sterile Neutrino Search Using Eight Years of Atmospheric Muon Neutrino Data from the IceCube Neutrino Observatory.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV^{2}. The best-fit point is found to be at sin^{2}(2θ_{24})=0.10 and Δm_{41}^{2}=4.5 eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.3×10^{19} eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19} eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18} eV is [5.66±0.03(stat)±1.40(syst)]×10^{53} erg Mpc^{-3}.