959 research outputs found
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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 km/s.
On the other hand, the wind velocity in the inner region where the NS is
located is only km/s, which is not expected on the basis of a
standard -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
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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., integrinα5ÎČ1, 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)
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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 TGFÎČ 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 TGFÎČ 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 11ÎČ-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 11ÎČ-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 (DELFIAÂź) 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 NexfinÂź 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 NexfinÂź 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 NexfinÂź, IBP and NIBP at five
intraoperative time-points. Pearson correlation coefficients, BlandâAltman
plots and trending ability of NexfinÂź 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/NexfinÂź (Pearsonâ=â0.75), which was better than the
correlation between IBP/NIBP (Pearsonâ=â0.70). BlandâAltman analysis of the
data showed that compared with IBP, there was a higher percentage error for
MAPNIBP (30%) compared with MAPNexfinÂź (27%). NexfinÂź and NIBP underestimated
systolic BP; NIBP also underestimated diastolic BP and MAP. Trending ability
for MAPNexfinÂź and MAPNIBP were comparable to IBP. Conclusion Non-invasive BP
measurement with NexfinÂź 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 (LVEFâ<â35%) 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 (pâ=â0.009
for nonparametric analysis of longitudinal data in a two-factorial design) and
incidence of postoperative renal dysfunction (67.9% vs. 94.4%; pâ=â0.033) 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; pâ=â0.046) 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
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