All eyes on PCS: analysis of the retinal microvasculature in patients with post-COVID syndrome-study protocol of a 1 year prospective case-control study.

Since widespread vaccination against COVID-19, the development of effective antiviral drugs, and the decreasing number of patients with COVID-19 in intensive care, the risk from SARS-CoV-2 infection appears less threatening. However, studies show that a significant number of patients suffer from long-term sequelae, even months after SARS-CoV-2 infection. The so-called post-COVID syndrome (PCS) often presents a diagnostic and treatment challenge for physicians. This study protocol describes the "All Eyes on PCS" study, which aims to investigate the retinal microvasculature in PCS patients and COVID-19-recovered patients to provide new insights into the pathophysiology of PCS. "All Eyes on PCS" is a prospective, case-control study with the primary objective of detecting endothelial dysfunction (ED) in patients with PCS. Therefore, we intend to recruit patients with PCS, fully SARS-CoV-2-infection-recovered (CR) participants, and SARS-CoV-2-infection-naïve (CN) participants. Baseline measurements will include: (1) patient-specific characteristics, (2) biochemistry, (3) retinal vessel analysis (RVA), (4) survey questionnaires as patient-reported outcomes measurements (PROMs), (5) optical coherence tomography (OCT), OCT angiography (OCTA), and adaptive optics (AO), (6) blood pressure recordings, (7) handgrip strength test. After 6 months, baseline measurements will be repeated in the PCS cohort, and after 1 year, a telephone query will be conducted to assess residual symptoms and treatment needs. The aim of this study is to gain insight into the pathophysiology of PCS and to provide an objective biomarker for diagnosis and treatment, while also creating a comprehensive clinical database of PCS patients.ClinicalTrials.gov Identifier: NCT05635552; Date: 2.12.2022.

Poly(arylene iminoborane)s, Analogues of Poly(arylene vinylene) with a BN-Doped Backbone: A Comprehensive Study.

Despite the great success of the concept of doping organic compounds with BN units to access new materials with tailored properties, its use in polymer chemistry has only been realized quite recently. Herein, we present a comprehensive study of oligo- and poly(arylene iminoborane)s comprising a backbone of phenylene or thiophene moieties, as well as combinations thereof, linked via B=N units. The novel polymers can be regarded as BN analogues of poly(p-phenylene vinylene) (PPV) or poly(thiophene vinylene) (PTV) or their copolymers. Our modular synthetic approach allowed us to prepare four polymers and 12 monodisperse oligomers with modulated electronic properties. Alternating electron-releasing diaminoarylene and electron-accepting diborylarylene building blocks gave rise to a pronounced donor-acceptor character. Effective π-conjugation over the arylene iminoborane backbone is evidenced by systematic bathochromic shifts of the low-energy UV-vis absorption maximum with increasing chain length, which is furthermore supported by crystallographic and computational investigations. Furthermore, all compounds investigated show emission of visible light in the solid state and aggregation-induced emission (AIE) behavior, due to the presence of partially flexible linear B=N linkages in the backbone.

Poly(thiophene iminoborane): A Poly(thiophene vinylene) (PTV) Analogue with a Fully BN-Doped Backbone.

An unprecedented poly(thiophene iminoborane)-a boron-nitrogen analogue of the well-established conjugated organic polymer poly(thiophene vinylene)-is presented. The polymer synthesis is achieved by selective Si/B exchange polycondensation of a 2,5-diborylthiophene with a 2,5-diaminothiophene derivative. For the latter, a facile synthetic strategy is devised, which makes this versatile, strongly electron-releasing building block easily accessible. The novel polymer and a series of monodisperse thiophene iminoborane oligomers reveal systematic bathochromic shifts in their absorption with increasing chain length, and thus extended π-conjugation over the BN units along the backbone, which is further supported by TD-DFT calculations.

Electrophilic activation of difunctional aminoboranes: B-N coupling versus intramolecular Cl/Me exchange.

Treatment of an N-silyl-B-chloro-aminoborane with substoichio-metric quantities of Me3SiOTf afforded B-N coupling, whereas activation with 5 mol% of Ag[Al{OC(CF3)3}4] led to Cl/Me exchange between the boron and the silicon center. Combined experimental and computational studies of the latter process support a chain reaction that is initiated by nucleation-limited chloride abstraction.

An Inverse Thermogelling Bioink Based on an ABA-Type Poly(2-oxazoline) Amphiphile.

Hydrogels are key components in several biomedical research areas such as drug delivery, tissue engineering, and biofabrication. Here, a novel ABA-type triblock copolymer comprising poly(2-methyl-2-oxazoline) as the hydrophilic A blocks and poly(2-phenethyl-2-oxazoline) as the aromatic and hydrophobic B block is introduced. Above the critical micelle concentration, the polymer self-assembles into small spherical polymer micelles with a hydrodynamic radius of approx 8-8.5 nm. Interestingly, this specific combination of hydrophilic and hydrophobic aromatic moieties leads to rapid thermoresponsive inverse gelation at polymer concentrations above a critical gelation concentration (20 wt %) into a macroporous hydrogel of densely packed micelles. This hydrogel exhibited pronounced viscoelastic solid-like properties, as well as extensive shear-thinning, rapid structure recovery, and good strain resistance properties. Excellent 3D-printability of the hydrogel at lower temperature opens a wide range of different applications, for example, in the field of biofabrication. In preliminary bioprinting experiments using NIH 3T3 cells, excellent cell viabilities of more than 95% were achieved. The particularly interesting feature of this novel material is that it can be used as a printing support in hybrid bioink systems and sacrificial bioink due to rapid dissolution at physiological conditions.

Inverse Thermogelation of Aqueous Triblock Copolymer Solutions into Macroporous Shear-Thinning 3D Printable Inks.

Amphiphilic block copolymers that undergo (reversible) physical gelation in aqueous media are of great interest in different areas including drug delivery, tissue engineering, regenerative medicine, and biofabrication. We investigated a small library of ABA-type triblock copolymers comprising poly(2-methyl-2-oxazoline) as the hydrophilic shell A and different aromatic poly(2-oxazoline)s and poly(2-oxazine)s cores B in an aqueous solution at different concentrations and temperatures. Interestingly, aqueous solutions of poly(2-methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazine)-block-poly(2-methyl-2-oxazoline) (PMeOx-b-PPheOzi-b-PMeOx) undergo inverse thermogelation below a critical temperature by forming a reversible nanoscale wormlike network. The viscoelastic properties of the resulting gel can be conveniently tailored by the concentration and the polymer composition. Storage moduli of up to 110 kPa could be obtained while the material retains shear-thinning and rapid self-healing properties. We demonstrate three-dimensional (3D) printing of excellently defined and shape-persistent 24-layered scaffolds at different aqueous concentrations to highlight its application potential, e.g., in the research area of biofabrication. A macroporous microstructure, which is stable throughout the printing process, could be confirmed via cryo-scanning electron microscopy (SEM) analysis. The absence of cytotoxicity even at very high concentrations opens a wide range of different applications for this first-in-class material in the field of biomaterials.

Catalyst-free room-temperature iClick reaction of molybdenum(ii) and tungsten(ii) azide complexes with electron-poor alkynes: structural preferences and kinetic studies.

Two isostructural and isoelectronic group VI azide complexes of the general formula [M(η3-allyl)(N3)(bpy)(CO)2] with M = Mo, W and bpy = 2,2'-bipyridine were prepared and fully characterized, including X-ray structure analysis. Both reacted smoothly with electron-poor alkynes such as dimethyl acetylenedicarboxylate (DMAD) and 4,4,4-trifluoro-2-butynoic acid ethyl ester in a catalyst-free room-temperature iClick [3 + 2] cycloaddition reaction. Reaction with phenyl(trifluoromethyl)acetylene, on the other hand, did not lead to any product formation. X-ray structures of the four triazolate complexes isolated showed the monodentate ligand to be N2-coordinated in all cases, which requires a 1,2-shift of the nitrogen from the terminal azide to the triazolate cycloaddition product. On the other hand, a 19F NMR spectroscopic study of the reaction of the fluorinated alkyne with the tungsten azide complex at 27 °C allowed detection of the N1-coordinated intermediate. With this method, the second-order rate constant was determined as (7.3 ± 0.1) × 10-2 M-1 s-1, which compares favorably with that of first-generation compounds such as difluorocyclooctyne (DIFO) used in the strain-promoted azide-alkyne cycloaddition (SPAAC). In contrast, the reaction of the molybdenum analogue was too fast to be studied with NMR methods. Alternatively, solution IR studies revealed pseudo-first order rate constants of 0.4 to 6.5 × 10-3 s-1, which increased in the order of Mo > W and F3C-C[triple bond, length as m-dash]C-COOEt > DMAD.

Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection.

BACKGROUND: The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established. METHODS: In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed. In addition to patient demographic data, we provide an overview of the FMT procedures and techniques used at different centers. RESULTS: Overall, 133 eligible patients from 33 centers were included, of which 64.7% were female (n = 86). The mean age was 75 years (interquartile range: 59.5-81.5). Administration via the duodenal route (n = 59; 44.4%) was the most frequently applied option, followed by colonic (n = 55; 41.1%), capsule (n = 13; 9.8%), and gastric administration (n = 4; 3.0%). Primary cure on day 30 and 90 was achieved in 84.2% (n = 101/120) and 78.3% (n = 72/92) of patients, respectively. Including re-treatment, secondary response was achieved in 87.5% (d 30; n = 105/120) and 85.9% (d 90; n = 79/92), respectively. Treatment- elated adverse events were documented in 16 patients (12.0%). CONCLUSION: FMT is a safe and effective treatment option for rCDI. However, FMT is currently available only in few centers in Germany, and treatment options vary from one center to another.

OCT Angiography Findings in Acute Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: To describe optical coherence tomography angiography (OCTA) findings in patients with acute central serous chorioretinopathy (CSC) compared to conventional imaging methods. PATIENTS AND METHODS: A consecutive series of 11 eyes from 10 healthy patients with acute CSC were included and underwent fluorescein angiography (FA), indocyanine green angiography (ICGA), OCT, fundus autofluorescence (FAF), and OCTA. Obtained OCTA images were evaluated for the presence of serous detachments of the neurosensory retina, leakage points, or other altered findings and compared to conventional imaging devices. RESULTS: In four out of 11 eyes, it was possible to detect detached retina adjacent to the leakage point in OCTA images, compared with four of 11 eyes using FA, five of 11 eyes using ICGA, 11 of 11 eyes using SD-OCT, and four of 11 eyes using FAF. In five out of 11 eyes, irregular flow patterns were observed on OCTA images through the choriocapillaris. OCTA images could not identify leakage points in any of the included eyes, compared with 11 out of 11 eyes on FA, five out of 11 eyes on ICGA, eight out of 11 eyes on SD-OCT, and zero out of 11 eyes on FAF. CONCLUSION: OCTA images of the superficial and deep retinal plexus, outer retina, and choriocapillaris did not reveal altered flow patterns directly associated with the leakage point in acute CSC. However, OCTA was able to visualize altered choroidal flow in some of the included eyes.

MR findings associated with positive distraction of the hip joint achieved by axial traction.

PURPOSE: To determine which MR-arthrography findings are associated with positive hip joint distraction. MATERIALS AND METHODS: One hundred patients with MR arthrography of the hip using axial traction were included. Traction was applied during the MR examination with an 8 kg (females) or 10 kg (males) water bag, attached to the ankle over a deflection pulley. Fifty patients showing joint space distraction were compared to an age- and gender-matched control group of 50 patients that did not show a joint distraction under axial traction. Two radiologists assessed the neck-shaft angle, lateral and anterior center-edge (CE) angles, CE angles in the transverse plane, extrusion index of the femoral head, acetabular depth, alpha angle, acetabular version, ligamentum teres, joint capsule and ligaments, iliopsoas tendon and the labrum. RESULTS: Mean joint space distraction in the study group was 0.9 ± 0.6 mm. Patients with positive joint space distraction had significantly higher neck-shaft angles (control group 131.6 ± 5.4°/study group 134.1 ± 6.1°, p < 0.05), smaller lateral CE angles (38.1 ± 5.9°/34.6 ± 7.2°, p < 0.05), smaller overall transverse CE angles (161.4 ± 9.9°/153.6 ± 9.6°, p < 0.001), smaller acetabular depth (4.1 ± 2.4 mm/5.8 ± 2.5 mm, p < 0.01), higher alpha angles (53.5 ± 7.8°/59.2 ± 10.1°, p < 0.01) and a thicker ligamentum teres (4.7 ± 1.4 mm/5.4 ± 1.8 mm, p < 0.05). The other parameters revealed no significant differences. ICC values for interobserver agreement were 0.71-0.95 and kappa values 0.43-0.92. CONCLUSION: Increased neck-shaft angles, small CE angles, small acetabular depth, higher alpha angles and a thick ligamentum teres are associated with positive joint distraction.

Evaluation of the hazard potentials of river suspended particulate matter and floodplain soils in the Rhine basin using chemical analysis and in vitro bioassays.

The purpose of the present study was to assess the hazard potentials of contaminated suspended particulate matter (SPM) sampled during a flood event for floodplain soils using in vitro bioassays and chemical analysis. Sediment-contact tests were performed to evaluate the direct exposure of organisms to native soils and SPM at two different trophic levels. For comparison, acetonic extracts were tested using both contact tests and additionally two cell-based biotests for cytotoxicity and Ah receptor-mediated activity (EROD-Assay). The sediment-contact tests were carried out with the dehydrogenase assay with Arthrobacter globiformis and the fish embryo assay with Danio rerio. The results of this study clearly document that native samples may well be significantly more effective than corresponding extracts in the bacteria contact assay or the fish embryo test. These results question the commonly accepted concept that acetonic extracts are likely to overestimate the toxicity of soil and SPM samples. Likewise, the priority organic compounds analyzed failed to fully explain the toxic potential of the samples. The outcomes of this study revealed the insufficient knowledge regarding the relationship between the different exposure pathways. Finally, there is concern about adverse effects by settling suspended particulate matter and remobilized sediments in frequently inundated floodplain soils due to an increase of the hazard potential, if compared with infrequently inundated floodplain soils. We showed that the settling of SPM and sediments revealed a significant impact on the dioxin-like potencies of riparian soils.

Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion.

PURPOSE: To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012. METHODS: Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was >18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice. RESULTS: Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of >25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition. CONCLUSIONS: DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice.

Calcaneal attachment of the plantar fascia: MR findings in asymptomatic volunteers.

PURPOSE: To determine the spectrum of magnetic resonance (MR) imaging findings at the calcaneal attachment of the plantar fascia in asymptomatic volunteers. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained from all subjects. MR imaging was performed in 77 asymptomatic volunteers (mean age, 48.0 years; age range, 23-83 years) with use of a 1.5-T system. There were 40 women (mean age, 49.0 years; age range, 24-83 years) and 37 men (mean age, 48.0 years; age range, 23-83 years). Signal intensity characteristics and thickness of the medial, central, and lateral fascicles of the plantar fascia were assessed independently by two radiologists. The presence of soft-tissue edema, bone marrow edema, and bone spur formation at the attachment of the plantar fascia was noted. Datasets were analyzed with inferential statistic procedures. RESULTS: The mean thickness of the plantar fascia was 0.6 mm (medial fascicle), 4.0 mm (central fascicle), and 2.3 mm (lateral fascicle). Increased signal intensity in the plantar fascia was seen with the T1-weighted sequence in 16 of the 77 volunteers (21%), the T2-weighted sequence in six (7.8%), and the short inversion time inversion-recovery sequence in six (7.8%). Soft-tissue edema was seen deep to the plantar fascia in five of the 77 volunteers (6.5%) and superficial to the plantar fascia in 16 (21%). A calcaneal spur was detected in 15 of the 77 volunteers (19%). Calcaneal bone marrow edema was present in four volunteers (5.2%). CONCLUSION: T1-weighted signal intensity changes in the plantar fascia, soft-tissue edema superficial to the plantar fascia, and calcaneal spurs are common findings in asymptomatic volunteers and should be used with caution in the diagnosis of plantar fasciitis. Increased signal intensity within the plantar fascia with fluid-sensitive sequences is uncommon in asymptomatic volunteers.

Cervical myelopathy due to chronic overshunting in a pediatric patient: case report and review of the literature.

We present a rare cause of cervical myelopathy produced by an engorged suboccipital epidural venous plexus due to chronic cerebrospinal fluid (CSF) overdrainage. A 17-year-old boy with obstructive hydrocephalus due to a retrocerebellar cyst and secondary implantation of a ventricloperitoneal shunt (VP-shunt) presented with progressive spastic tetraparesis. MRI imaging revealed myelopathy due to significant compression of the cervical spinal cord by engorged epidural veins. Further assessment at a low-pressure setting revealed a broken shunt valve. The VP-shunt valve was changed with an additional anti-siphon device leading to a gradual increase of the intracranial pressure (ICP). After intensive physiotherapy, the patient showed slight clinical improvement. Follow-up imaging within nine days showed distinct regression of the dilated venous plexus at the cranial-cervical junction (CCJ) with the resolution of cord compression. Engorgement of the epidural venous plexus should always be considered in the differential diagnosis of myelopathy in long-term shunt patients even when classical clinical and radiological signs of overshunting are missing.

Live monitoring of cargo release from peptide-based hybrid nanocapsules induced by enzyme cleavage.

The miniemulsion process is used as a new route for the preparation of enzyme-responsive nanocapsules with payload-release properties. Peptide-based hybrid nanocapsules are prepared via interfacial polyaddition containing a water-soluble dye that is efficiently encapsulated inside. The influence of the synthetic parameters as the functionality of the peptide and the nature of the dispersed phase on the structure of the nanocapsules were investigated. After redispersion in water, the enzymatic cleavage of the peptide sequence and the release of the fluorescent dye are both monitored in real time. This is evidenced because of the quenching FRET system framing the recognition site in the peptide sequence, and the fluorescence recovery of the self-quenched encapsulated dye respectively.

Mitotic spindle orients perpendicular to the forces imposed by dynamic shear.

Orientation of the division axis can determine cell fate in the presence of morphogenetic gradients. Understanding how mitotic cells integrate directional cues is therefore an important question in embryogenesis. Here, we investigate the effect of dynamic shear forces on confined mitotic cells. We found that human epithelial cells (hTERT-RPE1) as well as MC3T3 osteoblasts align their mitotic spindle perpendicular to the external force. Spindle orientation appears to be a consequence of cell elongation along the zero-force direction in response to the dynamic shear. This process is a nonlinear response to the strain amplitude, requires actomyosin activity and correlates with redistribution of myosin II. Mechanosteered cells divide normally, suggesting that this mechanism is compatible with biological functions.

Screening analysis of volatile organic contaminants in commercial inorganic coagulants used for drinking water treatment.

A method for quality screening is suggested to detect volatile impurities in inorganic coagulants that are used for drinking water treatment. Static headspace gas chromatography with mass spectrometry detection (HS-GCMS) is sensitive and selective to detect volatiles in low concentrations. This study has discovered that volatile organic impurities are detectable in ferric and aluminium-based coagulants which are used for drinking water treatment. For ferric chloride, 2-propanol was detected at a level of 17-24 microg ml(-1), acetone at 0.7-1.7 microg ml(-1), 1,1,1-trichloroacetone at 0.02-0.04 microg ml(-1), trichloromethane at 0.01-0.02 microg ml(-1) and toluene at 0.01-0.12 microg ml(-1). For ferric chloride sulfate, acetone was detected at a level of 0.12 microg ml(-1), 1,1,1-trichloroacetone at 0.06-0.08 microg ml(-1), trichloromethane at 0.13-0.23 microg ml(-1), bromodichloromethane at 0.04-0.06 microg ml(-1) and dibromochloromethane at 0.04-0.05 microg ml(-1). For aluminium hydroxide chloride, only trichloromethane was detectable, but below the method detection limits (MDL). Although the concentrations of these impurities in commercial coagulants are low, this observation is important and should have impact on water industries for them to pay attention to the chemicals they are using for drinking water production.

Formation of oxidation by-products of the iodinated X-ray contrast medium iomeprol during ozonation.

The present work describes the investigation of the formation of oxidation by-products of the iodinated X-ray contrast medium (ICM) iomeprol during ozonation in water treatment. Bench-scale investigations revealed that ICM can be partly oxidized during ozonation processes, whereas the ionic diatrizoic acid showed the lowest reactivity. Iomeprol, as a representative of ICM, was not fully mineralized during ozonation. Thus, unknown oxidation by-products were formed. Aqueous solutions of iomeprol were treated by ozonation in order to assess the formation of oxidation by-products. The by-products were characterized by different liquid chromatography methods including detection of single-stage mass spectra, product ion mass spectra, and induced in-source fragmentation for analysis of iodine containing oxidation by-products. Aldehyde and carbonyl containing compounds were proposed to be among the stable by-products. A derivatization step confirms that the aldehyde and carbonyl moieties are major functional groups in oxidation by-products of iomeprol. Furthermore, oxidation by-products of iomeprol were detected at the outlet of an ozone reactor at a full-scale waterworks. However, the toxicological relevance of the by-products is a major future research tasks.