Radiation-pressure cooling and optomechanical instability of a micro-mirror

Recent experimental progress in table-top experiments or gravitational-wave interferometers has enlightened the unique displacement sensitivity offered by optical interferometry. As the mirrors move in response to radiation pressure, higher power operation, though crucial for further sensitivity enhancement, will however increase quantum effects of radiation pressure, or even jeopardize the stable operation of the detuned cavities proposed for next-generation interferometers. The appearance of such optomechanical instabilities is the result of the nonlinear interplay between the motion of the mirrors and the optical field dynamics. In a detuned cavity indeed, the displacements of the mirror are coupled to intensity fluctuations, which modifies the effective dynamics of the mirror. Such "optical spring" effects have already been demonstrated on the mechanical damping of an electromagnetic waveguide with a moving wall, on the resonance frequency of a specially designed flexure oscillator, and through the optomechanical instability of a silica micro-toroidal resonator. We present here an experiment where a micro-mechanical resonator is used as a mirror in a very high-finesse optical cavity and its displacements monitored with an unprecedented sensitivity. By detuning the cavity, we have observed a drastic cooling of the micro-resonator by intracavity radiation pressure, down to an effective temperature of 10 K. We have also obtained an efficient heating for an opposite detuning, up to the observation of a radiation-pressure induced instability of the resonator. Further experimental progress and cryogenic operation may lead to the experimental observation of the quantum ground state of a mechanical resonator, either by passive or active cooling techniques

Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ((f)AABs) targeting G-protein coupled receptors (GPCR-(f)AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-(f)AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-(f)AABs that acted as receptor agonists. Some of those GPCR-(f)AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-(f)AAB detection). Other GPCR-(f)AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-(f)AABs identified in the blood of Long-COVID patients targeted the β(2)-adrenoceptor (β(2)-(f)AAB), the α1-adrenoceptor (α(1)-(f)AAB), the angiotensin II AT1-receptor (AT1-(f)AAB), and the nociceptin-like opioid receptor (NOC-(f)AAB). The negative chronotropic GPCR-(f)AABs identified targeted the muscarinic M(2)-receptor (M(2)-(f)AAB), the MAS-receptor (MAS-(f)AAB), and the ETA-receptor (ETA-(f)AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies

Agonistic autoantibodies against β2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients

PURPOSE: Agonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG. MATERIAL AND METHODS: Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb. RESULTS: (I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028). CONCLUSION: FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A

Patients with COVID-19: in the dark-NETs of neutrophils.

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19

Selenspiegel bei Glaukompatienten: eine Pilotstudie.

Hintergrund Spurenelemente können über oxidativen Stress vermittelte molekulare Interaktionen in die Pathogenese der Glaukomerkrankung eingreifen. Vor allem für das Spurenelement Selen (Se) wird eine Mitbeteiligung postuliert. Der Selengehalt im Serum wird unter anderem über die Ernährung gesteuert und unterliegt damit kulturellen und ethnischen Variabilitäten. Das Ziel der vorliegenden Studie war es, den Serumselenspiegel bei Patienten mit primärem Offenwinkelglaukom (pOWG) im Vergleich zu einer Kontrollgruppe zu analysieren. Diese Ergebnisse der vorliegenden deutschen Kohorte wurden auf mögliche Alters- und Gendereffekte hin untersucht sowie ins Verhältnis zu der bislang einzig beschriebenen Kohorte in den US gesetzt. Material und Methoden Die Selenkonzentration wurde von 39 Serumproben (22 pOWG, 17 Kontrollen) anhand der Inductively coupled Plasma-sector Field Mass Spectrometry (ICP-sf-MS) analysiert. Die statistische Analyse umfasste eine Kovarianz-, Perzentilenregressions-, Alters- und Genderanalyse. Ergebnisse Die Serumselenkonzentration (Ls-mean) betrug 134,86 µg/l für Patienten mit pOWG und 132,02 µg/l für die Kontrollgruppe. Der Serumselengehalt zwischen diesen beiden Gruppen zeigte keinen signifikanten Unterschied (p > 0,05). Jedoch war ein dezenter Alters- und Gendereffekt zu beobachten. Die Quantilanalyse erbrachte eine Reduktion der 1. Serumselenquantile mit ansteigendem Alter bei den Patienten mit pOWG im Gegensatz zu den Kontrollprobanden. Die Odds Ratio der 1. Quantile betrug 1,3 (jeweils in Bezug zur 2. und 3. Quantile). Zusammenfassung Der Serumselengehalt von Patienten mit pOWG zeigte sich als ca. halb so hoch wie der publizierte Wert der US-Literaturkohorte (Glaukom 209,11 ng/ml; Kontrolle 194,45 ng/ml). Zusätzlich war ein leichter Alters- und Gendereffekt zu beobachten

OCT angiography: Measurement of retinal macular microvasculature with spectralis II OCT angiography - reliability and reproducibility.

Aim: The aim of the present study was to investigate the reliability of macular microvasculature measurements in normal subjects by Heidelberg Spectralis II optical coherence tomography angiography (OCT-A) in combination with a newly made software. Subjects and Methods: This prospective study included 23 eyes of 23 persons from the Erlangen Glaucoma Registry (ISSN 2191-5008, CS-2011; NTC00494923). The subjects underwent a complete clinical, standardized ophthalmologic examination to rule out any eye disease. En face OCT-A imaging was done using Heidelberg Spectralis II OCT (Heidelberg, Germany). Images were recorded with a 15 x 15 degrees angle and a lateral resolution of 5.7 mu m/pixel, resulting in a retinal section of 2.9 x 2.9 mm. The Erlangen-Angio-Tool (EA-Tool) OCT-A application performed multiple segmentations, allowing analysis of the vessel density in 12 segments. The software was coded in MATLAB. Macular data on the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were exported into the application and analyzed separately. The EA-Tool calculated the percentage of "white area" in the "total area" of the region of interest, called vessel density. Foveolar avascular zones (FAZs) of the SVP, ICP, and DCP were calculated manually. To investigate the reproducibility of the new software, individual scans (SVP, ICP, and DCP) were analyzed twice with the EA-Tool and intraclass coefficients (ICCs) of the vessel density values were calculated. Statistical analysis was performed with SPSS version 21.0. Results: The mean vessel density of the SVP ranged between 30.4 and 33.5, that of the ICP between 20.9 and 24.7, and that of the DCP between 23.5 and 27.6. Bland-Altman plots showed a good reliability of two consecutive scans of each sector (S1-S12) in the SVP, ICP, and DCP. Testing reproducibility, no statistically significantly different sectorial coefficients of variation of the SVP, ICP, and DCP were observed (p > 0.05). The mean FAZ area of the SVP was 0.43 +/- 0.16 mm(2), that of the ICP 0.28 +/- 0.1 mm(2), and that of the DCP 0.44 +/- 0.12 mm(2). Conclusions: Spectralis OCT II, in combination with the semiautomated vessel density software EA-Tool, showed good or even excellent ICCs in 75% of all segments of the SVP, ICP, and DCP. The ICCs for the FAZ area in the SVP, ICP, and DCP were excellent