Hyperspectral Imaging of Wounds Reveals Augmented Tissue Oxygenation following Cold Physical Plasma Treatment in Vivo

Efficient vascularization of skin tissue supports wound healing in response to injury. This includes elevated blood circulation, tissue oxygenation, and perfusion. Cold physical plasma promotes wound healing in animal models and humans. Physical plasmas are multicomponent systems that generate several physicochemical effectors, such as ions, electrons, reactive oxygen and nitrogen species, and UV radiation. However, the consequences of plasma treatment on wound oxygenation and perfusion, vital processes to promote tissue regeneration, are largely unexplored. We used a novel hyperspectral imaging (HSI) system and a murine dermal full-thickness wound model in combination with kINPen argon plasma jet treatment to address this question. Plasma treatment promoted tissue oxygenation in superficial as well as deep (6 mm) layers of wound tissue. In addition to perfusion changes, we found a wound healing stage-dependent shift of tissue hemoglobin and tissue water index during reactive species-driven wound healing. Contactless, fast monitoring of medical parameters in real-time using HSI revealed a plasma-supporting effect in wound healing together with precise information about biological surface-specific features

Coupling hydrodynamics with comoving frame radiative transfer: II. Stellar wind stratification in the high-mass X-ray binary Vela X-1

CONTEXT: Vela X-1, a prototypical high mass X-ray binary (HMXB), hosts a neutron star (NS) in a close orbit around an early-B supergiant donor star. Accretion of the donor star's wind onto the NS powers its strong X-ray luminosity. To understand the physics of HMXBs, detailed knowledge about the donor star winds is required. AIMS: To gain a realistic picture of the donor star in Vela X-1, we constructed a hydrodynamically consistent atmosphere model describing the wind stratification while properly reproducing the observed donor spectrum. To investigate how X-ray illumination affects the stellar wind, we calculated additional models for different X-ray luminosity regimes. METHODS: We use the recently updated version of the PoWR code to consistently solve the hydrodynamic equation together with the statistical equations and the radiative transfer. RESULTS: The wind flow in Vela X-1 is driven by ions from various elements with Fe III and S III leading in the outer wind. The model-predicted mass-loss rate is in line with earlier empirical studies. The mass-loss rate is almost unaffected by the presence of the accreting NS in the wind. The terminal wind velocity is confirmed at $v_\infty \approx 600$ km/s. On the other hand, the wind velocity in the inner region where the NS is located is only $\approx 100$ km/s, which is not expected on the basis of a standard $\beta$-velocity law. In models with an enhanced level of X-rays, the velocity field in the outer wind can be altered. If the X-ray flux is too high, the acceleration breaks down because the ionization increases. CONCLUSIONS: Accounting for radiation hydrodynamics, our Vela X-1 donor atmosphere model reveals a low wind speed at the NS location, and it provides quantitative information on wind driving in this important HMXB.Comment: 19 pages, 10 figures, accepted for publication in Astronomy & Astrophysic

Gas plasma-spurred wound healing is accompanied by regulation of focal adhesion, matrix remodeling, and tissue oxygenation

In response to injury, efficient migration of skin cells to rapidly close the wound and restore barrier function requires a range of coordinated processes in cell spreading and migration. Gas plasma technology produces therapeutic reactive species that promote skin regeneration by driving proliferation and angiogenesis. However, the underlying molecular mechanisms regulating gas plasma-aided cell adhesion and matrix remodeling essential for wound closure remain elusive. Here, we combined in vitro analyses in primary dermal fibroblasts isolated from murine skin with in vivo studies in a murine wound model to demonstrate that gas plasma treatment changed phosphorylation of signaling molecules such as focal adhesion kinase and paxillin α in adhesion-associated complexes. In addition to cell spreading and migration, gas plasma exposure affected cell surface adhesion receptors (e.g., integrinα5β1, syndecan 4), structural proteins (e.g., vinculin, talin, actin), and transcription of genes associated with differentiation markers of fibroblasts-to-myofibroblasts and epithelial-to-mesenchymal transition, cellular protrusions, fibronectin fibrillogenesis, matrix metabolism, and matrix metalloproteinase activity. Finally, we documented that gas plasma exposure increased tissue oxygenation and skin perfusion during ROS-driven wound healing. Altogether, these results provide critical insights into the molecular machinery of gas plasma-assisted wound healing mechanisms

Maximum Likelihood Training of Autoencoders

Maximum likelihood training has favorable statistical properties and is popular for generative modeling, especially with normalizing flows. On the other hand, generative autoencoders promise to be more efficient than normalizing flows due to the manifold hypothesis. In this work, we introduce successful maximum likelihood training of unconstrained autoencoders for the first time, bringing the two paradigms together. To do so, we identify and overcome two challenges: Firstly, existing maximum likelihood estimators for free-form networks are unacceptably slow, relying on iteration schemes whose cost scales linearly with latent dimension. We introduce an improved estimator which eliminates iteration, resulting in constant cost (roughly double the runtime per batch of a vanilla autoencoder). Secondly, we demonstrate that naively applying maximum likelihood to autoencoders can lead to divergent solutions and use this insight to motivate a stable maximum likelihood training objective. We perform extensive experiments on toy, tabular and image data, demonstrating the competitive performance of the resulting model. We call our model the maximum likelihood autoencoder (MLAE)

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion

Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune-infiltrates of CD8+ cytotoxic T-cells and dendritic cells. T-cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat-shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo

Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease

Rho-family GTPases like RhoA and Rac-1 are potent regulators of cellular signaling that control gene expression, migration and inflammation. Activation of Rho-GTPases has been linked to podocyte dysfunction, a feature of chronic kidney diseases (CKD). We investigated the effect of Rac-1 and Rho kinase (ROCK) inhibition on progressive renal failure in mice and studied the underlying mechanisms in podocytes. SV129 mice were subjected to 5/6-nephrectomy which resulted in arterial hypertension and albuminuria. Subgroups of animals were treated with the Rac-1 inhibitor EHT1846, the ROCK inhibitor SAR407899 and the ACE inhibitor Ramipril. Only Ramipril reduced hypertension. In contrast, all inhibitors markedly attenuated albumin excretion as well as glomerular and tubulo-interstitial damage. The combination of SAR407899 and Ramipril was more effective in preventing albuminuria than Ramipril alone. To study the involved mechanisms, podocytes were cultured from SV129 mice and exposed to static stretch in the Flexcell device. This activated RhoA and Rac-1 and led via TGFβ to apoptosis and a switch of the cells into a more mesenchymal phenotype, as evident from loss of WT-1 and nephrin and induction of α-SMA and fibronectin expression. Rac-1 and ROCK inhibition as well as blockade of TGFβ dramatically attenuated all these responses. This suggests that Rac-1 and RhoA are mediators of podocyte dysfunction in CKD. Inhibition of Rho-GTPases may be a novel approach for the treatment of CKD

Neonatal screening: identification of children with 11β-hydroxylase deficiency by second-tier testing

21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing.Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol.In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal.Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay

Comparison of the non-invasive Nexfin® monitor with conventional methods for the measurement of arterial blood pressure in moderate risk orthopaedic surgery patients

Objective Continuous invasive arterial blood pressure (IBP) monitoring remains the gold standard for BP measurement, but traditional oscillometric non- invasive intermittent pressure (NIBP) measurement is used in most low-to- moderate risk procedures. This study compared non-invasive continuous arterial BP measurement using a Nexfin® monitor with NIBP and IBP monitors. Methods This was a single-centre, prospective, pilot study in patients scheduled for elective orthopaedic surgery. Systolic BP, diastolic BP and mean arterial blood pressure (MAP) were measured by Nexfin®, IBP and NIBP at five intraoperative time-points. Pearson correlation coefficients, Bland–Altman plots and trending ability of Nexfin® measurements were used as criteria for success in the investigation of measurement reliability. Results A total of 20 patients were enrolled in the study. For MAP, there was a sufficient correlation between IBP/Nexfin® (Pearson = 0.75), which was better than the correlation between IBP/NIBP (Pearson = 0.70). Bland–Altman analysis of the data showed that compared with IBP, there was a higher percentage error for MAPNIBP (30%) compared with MAPNexfin® (27%). Nexfin® and NIBP underestimated systolic BP; NIBP also underestimated diastolic BP and MAP. Trending ability for MAPNexfin® and MAPNIBP were comparable to IBP. Conclusion Non-invasive BP measurement with Nexfin® was comparable with IBP and tended to be more precise than NIBP

a retrospective analysis

Background Several animal studies suggest beneficial effects on kidney function upon administration of levosimendan. As recent data from clinical studies are heterogeneous, we sought to investigate whether levosimendan is associated with improved postoperative kidney function in cardiac surgery patients with respect to timing of its administration. Methods Retrospective, single centre, observational analysis at a university hospital in Berlin, Germany. All adult patients without preoperative renal dysfunction that underwent coronary artery bypass grafting and/or valve reconstruction/replacement between 01/01/2007 and 31/12/2011 were considered for analyses. Results Out of 1.095 included patients, 46 patients were treated with levosimendan due to a severely reduced left ventricular systolic function preoperatively (LVEF < 35%) and/or clinical signs of a low cardiac output syndrome. Sixty-one percent received the drug whilst in the OR, 39% after postoperative intensive care unit admission. When levosimendan was given immediately after anaesthesia induction, creatinine plasma levels (p = 0.009 for nonparametric analysis of longitudinal data in a two-factorial design) and incidence of postoperative renal dysfunction (67.9% vs. 94.4%; p = 0.033) were significantly reduced in contrast to a later start of treatment. In addition, duration of renal replacement therapy was significantly shorter (79 [35;332] vs. 272 [132;703] minutes; p = 0.046) in that group. Conclusions Postoperative kidney dysfunction is a common condition in patients under going cardiac surgery. Patients with severely reduced left ventricular function and/or clinical signs of a low cardiac output syndrome who preoperatively presented with a normal kidney function may benefit from an early start of levosimendan administration, i.e. immediately after anaesthesia

Neurosurgical Care during the COVID-19 Pandemic in Central Germany: A Retrospective Single Center Study of the Second Wave

The healthcare system has been placed under an enormous burden by the SARS-CoV-2 (COVID-19) pandemic. In addition to the challenge of providing sufficient care for COVID-19 patients, there is also a need to ensure adequate care for non-COVID-19 patients. We investigated neurosurgical care in a university hospital during the pandemic. We examined the second wave of the pandemic from 1 October 2020 to 15 March 2021 in this retrospective single-center study and compared it to a pre-pandemic period from 1 October 2019 to 15 March 2020. Any neurosurgical intervention, along with patient- and treatment-dependent factors, were recorded. We also examined perioperative complications and unplanned readmissions. A statistical comparison of the study groups was performed. We treated 535 patients with a total of 602 neurosurgical surgeries during the pandemic. This compares to 602 patients with 717 surgeries during the pre-pandemic period. There were 67 fewer patients (reduction to 88.87%) admitted and 115 fewer surgeries (reduction to 83.96%) performed, which were essentially highly elective procedures, such as cervical spinal stenosis, intracranial neurinomas, and peripheral nerve lesions. Regarding complication rates and unplanned readmissions, there was no significant difference between the COVID-19 pandemic and the non-pandemic patient group. Operative capacities were slightly reduced to 88% due to the pandemic. Nevertheless, comprehensive emergency and elective care was guaranteed in our university hospital. This speaks for the sufficient resources and high-quality processes that existed even before the pandemic