Telephone follow-up after outpatient nail surgery - a retrospective analysis.

BACKGROUND: One of the areas of care in dermatosurgery is the surgical treatment of diseases of the nail organ. Side effects and complications after nail surgery were investigated by telephone follow-up (TFU), and its suitability for postoperative monitoring and consultation was assessed. PATIENTS AND METHODS: All patients who underwent nail surgery at the Department of Dermatology at the Ludwigshafen City Hospital from October 2019 to December 2021 in outpatient setting were contacted by telephone on the second to third postoperative day and questioned in a standardized manner about postoperative complaints and counselled if necessary. RESULTS: A total of 100 cases were followed up. The most common procedures performed were phenol matricectomy (41%), nail avulsion (16%), and nail matrix biopsies (9%). 50% and 21% of patients reported pain on the day of the procedure and the day after surgery, respectively. After nail avulsion, pain was statistically significantly more frequently reported on the day following the procedure and pain medication was statistically significantly more frequently required (p  =  0.002). Serious adverse events did not occur after nail surgery. 10% of the respondents raised specific questions and needed counseling by TFU. CONCLUSIONS: All nail surgeries were well tolerated in the outpatient setting. Pain was the most common side effect, although only half of all patients reported pain on the day of surgery and only 21% on the day after the procedure. The TFU proved to be an effective and practical as well as easy to establish method for postoperative follow-up and consultation after outpatient nail surgery.

Effects of the COVID-19 pandemic on inpatient skin surgery in Germany: results of the DESSI-survey.

BACKGROUND: The aim of the survey was to investigate a possible impairment of inpatient dermatological and dermatosurgical care in Germany due to the COVID-19 pandemic. METHODS: An online survey on the impact of pandemic-related measures on inpatient care was sent to all German dermatology clinics. Only one person per clinic was asked to participate. Data analysis was mainly descriptive. Differences between university hospitals and non-university hospitals were calculated using the Chi-square test. RESULTS: From the 113 dermatological clinics with inpatient care, we received 45 (39.8%) at least partially completed questionnaires. Of these, 25 (55.6%) came from university hospitals, 18 (40.0%) from teaching hospitals of a university, 1 (2.2%) from a non-teaching hospital, and 1 (2.2%) from a participant who did not provide any information on his facility. More than half of survey participants (57.8%) reported that many elective skin surgeries had to be canceled at their clinics at the beginning of the COVID-19 pandemic. However, most of the clinics (75.6%) were able to perform medically necessary surgeries (such as for malignant melanoma). Only 28.9% (13/45) of participants reported that skin surgery in their clinics returned to full strength after the COVID-19 pandemic. There was no statistically significant difference between university hospitals and non-university hospitals regarding the influence of COVID-19-related restrictions. CONCLUSIONS: Despite their heterogeneity, the results of the survey show an overall clear and long-term pandemic-related impairment of inpatient dermatology and skin surgery in Germany.

Nonlinear amplification of microwave signals in spin-torque oscillators.

Spintronics-based microwave devices, such as oscillators and detectors, have been the subject of intensive investigation in recent years owing to the potential reductions in size and power consumption. However, only a few concepts for spintronic amplifiers have been proposed, typically requiring complex device configurations or material stacks. Here, we demonstrate a spintronic amplifier based on two-terminal magnetic tunnel junctions (MTJs) produced with CMOS-compatible material stacks that have already been used for spin-transfer torque memories. We achieve a record gain (|S11 | > 2) for input power on the order of nW (<-40 dBm) at an appropriate choice of the bias field direction and amplitude. Based on micromagnetic simulations and experiments, we describe the fundamental aspects driving the amplification and show the key role of the co-existence in microwave emissions of a dynamic state of the MTJ excited by a dc current and the injection locking mode driven by the microwave input signal. Our work provides a way to develop a class of compact amplifiers that can impact the design of the next generation of spintronics-CMOS hybrid systems.

Protocol to differentiate monolayer human induced pluripotent stem cells into inflammatory responsive astrocytes.

Glia, and in particular astrocytes, are one of the major players in neurological and neuroinflammatory disorders. Here, we present a protocol to efficiently generate inflammatory responsive astrocytes from human induced pluripotent stem cells in a monolayer culture. We describe steps for neural differentiation to reach a homogeneous population of neural progenitor cells, followed by their differentiation into neural/glial progenitors. Finally, we detail enrichment to a 90% pure inflammatory responsive astrocyte population. For complete details on the use and execution of this protocol, please refer to Giordano et al.1.

Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity.

The interferon-induced transmembrane proteins (IFITM) are implicated in several biological processes, including antiviral defense, but their modes of action remain debated. Here, taking advantage of pseudotyped viral entry assays and replicating viruses, we uncover the requirement of host co-factors for endosomal antiviral inhibition through high-throughput proteomics and lipidomics in cellular models of IFITM restriction. Unlike plasma membrane (PM)-localized IFITM restriction that targets infectious SARS-CoV2 and other PM-fusing viral envelopes, inhibition of endosomal viral entry depends on lysines within the conserved IFITM intracellular loop. These residues recruit Phosphatidylinositol 3,4,5-trisphosphate (PIP3) that we show here to be required for endosomal IFITM activity. We identify PIP3 as an interferon-inducible phospholipid that acts as a rheostat for endosomal antiviral immunity. PIP3 levels correlated with the potency of endosomal IFITM restriction and exogenous PIP3 enhanced inhibition of endocytic viruses, including the recent SARS-CoV2 Omicron variant. Together, our results identify PIP3 as a critical regulator of endosomal IFITM restriction linking it to the Pi3K/Akt/mTORC pathway and elucidate cell-compartment-specific antiviral mechanisms with potential relevance for the development of broadly acting antiviral strategies.

Tuning the Coexistence Regime of Incomplete and Tubular Skyrmions in Ferromagnetic/Ferrimagnetic/Ferromagnetic Trilayers.

The development of skyrmionic devices requires a suitable tuning of material parameters to stabilize skyrmions and control their density. It has been demonstrated recently that different skyrmion types can be simultaneously stabilized at room temperature in heterostructures involving ferromagnets, ferrimagnets, and heavy metals, offering a new platform of coding binary information in the type of skyrmion instead of the presence/absence of skyrmions. Here, we tune the energy landscape of the two skyrmion types in such heterostructures by engineering the geometrical and material parameters of the individual layers. We find that a fine adjustment of the ferromagnetic layer thickness, and thus its magnetic anisotropy, allows the trilayer system to support either one of the skyrmion types or the coexistence of both and with varying densities.

DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières syndrome astrocytes.

Aberrant induction of type I IFN is a hallmark of the inherited encephalopathy Aicardi-Goutières syndrome (AGS), but the mechanisms triggering disease in the human central nervous system (CNS) remain elusive. Here, we generated human models of AGS using genetically modified and patient-derived pluripotent stem cells harboring TREX1 or RNASEH2B loss-of-function alleles. Genome-wide transcriptomic analysis reveals that spontaneous proinflammatory activation in AGS astrocytes initiates signaling cascades impacting multiple CNS cell subsets analyzed at the single-cell level. We identify accumulating DNA damage, with elevated R-loop and micronuclei formation, as a driver of STING- and NLRP3-related inflammatory responses leading to the secretion of neurotoxic mediators. Importantly, pharmacological inhibition of proapoptotic or inflammatory cascades in AGS astrocytes prevents neurotoxicity without apparent impact on their increased type I IFN responses. Together, our work identifies DNA damage as a major driver of neurotoxic inflammation in AGS astrocytes, suggests a role for AGS gene products in R-loop homeostasis, and identifies common denominators of disease that can be targeted to prevent astrocyte-mediated neurotoxicity in AGS.

Coexistence of distinct skyrmion phases observed in hybrid ferromagnetic/ferrimagnetic multilayers.

Materials hosting magnetic skyrmions at room temperature could enable compact and energetically-efficient storage such as racetrack memories, where information is coded by the presence/absence of skyrmions forming a moving chain through the device. The skyrmion Hall effect leading to their annihilation at the racetrack edges can be suppressed, for example, by antiferromagnetically-coupled skyrmions. However, avoiding modifications of the inter-skyrmion distances remains challenging. As a solution, a chain of bits could also be encoded by two different solitons, such as a skyrmion and a chiral bobber, with the limitation that it has solely been realized in B20-type materials at low temperatures. Here, we demonstrate that a hybrid ferro/ferri/ferromagnetic multilayer system can host two distinct skyrmion phases at room temperature, namely tubular and partial skyrmions. Furthermore, the tubular skyrmion can be converted into a partial skyrmion. Such systems may serve as a platform for designing memory applications using distinct skyrmion types.

Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing In Human Hematopoietic Stem Cells.

Innate immune factors may restrict hematopoietic stem cell (HSC) genetic engineering and contribute to broad individual variability in gene therapy outcomes. Here, we show that HSCs harbor an early, constitutively active innate immune block to lentiviral transduction that can be efficiently overcome by cyclosporine H (CsH). CsH potently enhances gene transfer and editing in human long-term repopulating HSCs by inhibiting interferon-induced transmembrane protein 3 (IFITM3), which potently restricts VSV glycoprotein-mediated vector entry. Importantly, individual variability in endogenous IFITM3 levels correlated with permissiveness of HSCs to lentiviral transduction, suggesting that CsH treatment will be useful for improving ex vivo gene therapy and standardizing HSC transduction across patients. Overall, our work unravels the involvement of innate pathogen recognition molecules in immune blocks to gene correction in primary human HSCs and highlights how these roadblocks can be overcome to develop innovative cell and gene therapies.

The Pan European Emesis Registry (PEER): a critical appraisal of the Italian experience.

PURPOSE: Data from a large European prospective observational study were analysed to describe the antiemetic prescribing pattern for chemotherapy-induced nausea and vomiting (CINV) in Italian clinical practice. METHODS: Post hoc analysis of the Pan European Emesis Registry in chemo-naïve adults initiating single-day highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer. RESULTS: A total of 211 eligible patients were enrolled in the Italian centres, 180 were included in the analyses for cycle 1; 50·6% received MEC. The use of guideline-consistent CINV prophylaxis (GCCP) varied substantially between acute and delayed phases (54·4% during the acute phase vs. 29·4% in the overall 120-hour study period, acute plus delayed phases). Neurokinin-1 receptor antagonist was added to the prophylaxis with dexamethasone+5-hydroxytryptamine type 3 receptor antagonists in only 11·1% of patients (vs. 57·2% of the entire European study population). In the GCCP group, the complete response rate was significantly higher than that recorded in the guideline-inconsistent CINV prophylaxis (GICP) group (75·5 vs. 53·5%, P = 0·006). CONCLUSION: The proportion of guideline-consistent antiemetic therapy was quite low in the Italian population as it was in the overall European population. The implementation of specific guidelines' recommendations for chemotherapeutic regimens administered according to standard protocols could be considered as a means to reduce the burden of CINV.

On the use of mathematical models to build the design space for the primary drying phase of a pharmaceutical lyophilization process.

The aim of this article is to show a procedure to build the design space for the primary drying of a pharmaceuticals lyophilization process. Mathematical simulation of the process is used to identify the operating conditions that allow preserving product quality and meeting operating constraints posed by the equipment. In fact, product temperature has to be maintained below a limit value throughout the operation, and the sublimation flux has to be lower than the maximum value allowed by the capacity of the condenser, besides avoiding choking flow in the duct connecting the drying chamber to the condenser. Few experimental runs are required to get the values of the parameters of the model: the dynamic parameters estimation algorithm, an advanced tool based on the pressure rise test, is used to this purpose. A simple procedure is proposed to take into account parameters uncertainty and, thus, it is possible to find the recipes that allow fulfilling the process constraints within the required uncertainty range. The same approach can be effective to take into account the heterogeneity of the batch when designing the freeze-drying recipe.

On the automaticity and flexibility of covert attention: a speed-accuracy trade-off analysis.

Exogenous covert attention improves discriminability and accelerates the rate of visual information processing (M. Carrasco & B. McElree, 2001). Here we investigated and compared the effects of both endogenous (sustained) and exogenous (transient) covert attention. Specifically, we directed attention via spatial cues and evaluated the automaticity and flexibility of exogenous and endogenous attention by manipulating cue validity in conjunction with a response-signal speed-accuracy trade-off (SAT) procedure, which provides conjoint measures of discriminability and information accrual. To investigate whether discriminability and rate of information processing differ as a function of cue validity (chance to 100%), we compared how both types of attention affect performance while keeping experimental conditions constant. With endogenous attention, both the observed benefits (valid-cue) and the costs (invalid-cue) increased with cue validity. However, with exogenous attention, the benefits and costs in both discriminability and processing speed were similar across cue validity conditions. These results provide compelling time-course evidence that whereas endogenous attention can be flexibly allocated according to cue validity, exogenous attention is automatic and unaffected by cue validity.

Attention speeds processing across eccentricity: feature and conjunction searches.

We investigated whether the effect of covert attention on information accrual varies with eccentricity (4 degrees vs 9 degrees) and the complexity of the visual search task (feature vs conjunction). We used speed-accuracy tradeoff procedures to derive conjoint measures of the speed of information processing and accuracy in each search task. Information processing was slower with more complex conjunction searches than with simpler feature searches, and overall it was faster at peripheral (9 degrees) than parafoveal (4 degrees) locations in both search types. Covert attention increased discriminability and accelerated information accrual at both eccentricities, and the magnitude of this attentional effect was the same for both feature (simple) and conjunction (complex) searches. Interestingly, in contrast to the compensatory effect of covert attention on information processing at iso-eccentric locations (temporal performance fields), covert attention did not eliminate speed differences across eccentricity.

Temporal performance fields: visual and attentional factors.

This study is the first to investigate: (a) 'temporal performance fields,' whether the speed of information accrual differs for different locations at a fixed eccentricity, and (b) whether covert attention modulates temporal dynamics differentially at isoeccentric locations. Using the speed accuracy tradeoff (SAT) procedure, we derived conjoint measures of how isoeccentric locations and precueing targets location affect speed and accuracy in a search task. The results demonstrate the existence of temporal performance fields, analogous to spatial performance fields: information accrual was fastest for target on the horizontal meridian, intermediate for targets at the intercardinal locations, slow for targets on the vertical meridian, and slowest for targets at the North (N) location (accrual time pattern: E&WS>intercardinal>E&W). Hence, the compensatory effect of attention eliminated the temporal asymmetries across isoeccentric locations.

Skeletal muscle metabolism in physiology and in cancer disease.

Skeletal muscle is a tissue of high demand and it accounts for most of daily energy consumption. The classical concept of energy metabolism in skeletal muscle has been profoundly modified on the basis of studies showing the influence of additional factors (i.e., uncoupling proteins (UCPs) and peroxisome proliferator activated receptors (PPARs)) controlling parameters, such as substrate availability, cellular enzymes, carrier proteins, and proton leak, able to affect glycolysis, nutrient oxidation, and protein degradation. This extremely balanced system is greatly altered by cancer disease that can induce muscle cachexia with significant deleterious consequences and results in muscle wasting and weakness, delaying or preventing ambulation, and rehabilitation in catabolic patients.

Speed of visual processing increases with eccentricity.

The visual system has a duplex design to meet conflicting environmental demands: the fovea has the resolution required to process fine spatial information, but the periphery is more sensitive to temporal properties. To investigate whether the periphery's sensitivity is partly due to the speed with which information is processed, we measured the full timecourse of visual information processing by deriving joint measures of discriminability and speed, and found that speed of information processing varies with eccentricity: processing was faster when same-size stimuli appeared at 9 degrees than 4 degrees eccentricity, and this difference was attenuated when the 9 degrees stimuli were magnified to equate cortical representation size. At the same eccentricity, larger stimuli are processed more slowly. These temporal differences are greater than expected from neurophysiological constraints.

Interaction of the ADP-ribosylating enzyme from the hyperthermophilic archaeon S. solfataricus with DNA and ss-oligo deoxy ribonucleotides.

The DNA-binding ability of the poly-ADPribose polymerase-like enzyme from the extremely thermophilic archaeon Sulfolobus solfataricus was determined in the presence of genomic DNA or single stranded oligodeoxyribonucleotides. The thermozyme protected homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induced structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA. However, enzyme activity was slightly increased by DNA. Competition assays demonstrated that the protein interacted also with heterologous DNA. In order to characterize further the DNA binding properties of the archaeal enzyme, various ss-oligodeoxyribonucleotides of different base composition, lengths (12-mer to 24-mer) and structure (linear and circular) were used for fluorescence titration measurements. Intrinsic fluorescence of the archaeal protein due to tryptophan (excitation at 295 nm) was measured in the presence of each oligomer at 60 degrees C. Changes of tryptophan fluorescence were induced by all compounds in the same range of base number per enzyme molecule, but independently from the structural features of oligonucleotides, although the protein exhibited a slight preference for those adenine-rich and circular. The binding affinities were comparable for all oligomers, with intrinsic association constants of the same order of magnitude (K=10(6) M(-1)) in 0.01 M Na-phosphate buffer, pH 8.0, and accounted for a "non-specific" binding protein. Circular dichroism analysis showed that at 60 degrees C the native protein was better organized in a secondary structure than at 20 degrees C. Upon addition of oligonucleotides, enzyme structure was further stabilized and changed towards a beta-conformation. This effect was more marked with the circular oligomer. The analysed oligodeoxyribonucleotides slightly enhanced enzyme activity with the maximal increase of 50% as compared to the control. No activation was observed with the circular oligomer.

High stability binding of poly(ADPribose) polymerase-like thermozyme from S. solfataricus with circular DNA.

The poly(ADPribose) polymerase-like thermozyme from the hyperthermophilic archaeon S. solfataricus was found to bind DNA with high affinity and non-specifically. Binding was independent of base composition and length of the nucleic acid, and the protein showed a slight preference for the circular structure. By using pCMV-Neo-Bam plasmid as experimental model, the behaviour of the thermozyme upon binding with either circular or linear plasmid was analyzed. pCMV-Neo-Bam has a single HindIII site that allows to obtain the linear structure after digestion with the restriction enzyme. Intrinsic tryptophan-dependent fluorescence of poly(ADPribose) polymerase-like thermozyme noticeably changed upon addition of either circular or linear plasmid, showing the same binding affinity (K=2 x 10(9) M-1). However, experiments of protection against temperature and DNase I gave evidence that the thermozyme formed more stable complexes with the circular structure than with the linear pCMV-Neo-Bam. Increasing temperature at various DNA/protein ratios had a double effect to reduce the amount of circular DNA undergoing denaturation and to split the melting point towards higher temperatures. Nil or irrelevant effect was observed with the linear form. Similarly, DNase acted preferentially on the linear plasmid/protein complexes, producing an extensive digestion even at high protein/DNA ratios, whereas the circular plasmid was protected by the thermozyme in a dose-dependent manner. The complexes formed by archaeal poly(ADPribose) polymerase (PARPss) with the circular plasmid were visualized by bandshift experiments both with ethidium bromide staining and by labelling the circular plasmid with 32P. The stability of complexes was tested as a function of enzyme concentration and in the presence of a cold competitor and of 0.1% SDS. From the performed experiments, a number of 3-10 base pairs bound per molecule of enzyme was calculated, indicating a high frequency of binding. The presence of circular DNA was also able to increase by 80% the poly(ADPribose)polymerase-like activity, as compared to 25% activation induced by the linear pCMV-Neo-Bam.