A novel and universal method for microRNA RT-qPCR data normalization

Gene expression analysis of microRNA molecules is becoming increasingly important. In this study we assess the use of the mean expression value of all expressed microRNAs in a given sample as a normalization factor for microRNA real-time quantitative PCR data and compare its performance to the currently adopted approach. We demonstrate that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes

Toward a Progressive Geopolitical EU: Principles and Recommendations

Having coined the term “geopolitical Commission” in her maiden speech as Commission president, Ursula von der Leyen more recently declared that the EU has now matured into a geopolitical union. This purported coming of age has occurred against the backdrop of a major hardening of the global political order. Re-emerging systemic rivalries are jeopardising global supply chains and multilateralism, whilst Russia’s aggression is a threat to EU and global security. All the while, the climate crisis is accelerating. However, as the tenure of the first geopolitical Commission comes to an end, competition and conflict, rather than cooperation, appear to define and frame the EU’s geopolitical turn. With the 2024 European elections on the horizon, this report formulates elements of what a progressive geopolitical EU could entail in the coming years

Cytochrome cM decreases photosynthesis under photomixotrophy in Synechocystis sp. PCC 6803

Photomixotrophy is a metabolic state that enables photosynthetic microorganisms to simultaneously perform photosynthesis and metabolism of imported organic carbon substrates. This process is complicated in cyanobacteria, since many, including Synechocystis sp. PCC 6803, conduct photosynthesis and respiration in an interlinked thylakoid membrane electron transport chain. Under photomixotrophy, the cell must therefore tightly regulate electron fluxes from photosynthetic and respiratory complexes. In this study, we demonstrate, via characterization of photosynthetic apparatus and the proteome, that photomixotrophic growth results in a gradual inhibition of QA- reoxidation in wild-type Synechocystis, which largely decreases photosynthesis over 3 d of growth. This process is circumvented by deleting the gene encoding cytochrome cM (CytM), a cryptic c-type heme protein widespread in cyanobacteria. The ΔCytM strain maintained active photosynthesis over the 3-d period, demonstrated by high photosynthetic O2 and CO2 fluxes and effective yields of PSI and PSII. Overall, this resulted in a higher growth rate compared to that of the wild type, which was maintained by accumulation of proteins involved in phosphate and metal uptake, and cofactor biosynthetic enzymes. While the exact role of CytM has not been determined, a mutant deficient in the thylakoid-localized respiratory terminal oxidases and CytM (ΔCox/Cyd/CytM) displayed a phenotype similar to that of ΔCytM under photomixotrophy. This, in combination with other physiological data, and in contrast to a previous hypothesis, suggests that CytM does not transfer electrons to these complexes. In summary, our data suggest that CytM may have a regulatory role in photomixotrophy by modulating the photosynthetic capacity of cells

Vitamin A deficiency retinopathy related to medical interventions in a Swiss cohort: a case series

AIMS OF THE STUDY: Vitamin A deficiency retinopathy is a potentially blinding disease. In developed countries, vitamin A deficiency due to malnutrition is rare. However, vitamin A deficiency can be caused by malabsorption resulting from bowel resection or medication. In this retrospective study, we present five cases of vitamin A deficiency retinopathy related to malabsorption secondary to medical interventions. METHODS: Electronic charts over a ten-year period (2012–2022) were screened for vitamin A deficiency retinopathy. Only patients with vitamin A deficiency confirmed by laboratory tests were included. Symptoms, medical history, visual acuity, optical coherence tomography, fundus autofluorescence, electrophysiological examination, and vitamin A levels were reviewed. RESULTS: Five eligible cases were identified. Median age was 44.7 years (range 22.2–88.9), median duration of ocular symptoms prior to diagnosis was 14 months, and median visual acuity was 1.0 (range 0.5–1.0, Snellen, decimal). Three patients had a history of bariatric surgery, one patient had a small bowel resection and was on octreotide treatment, and one patient suffered from cystic fibrosis and had a history of small bowel resection and severe hepatopathy. Optical coherence tomography showed various abnormalities, including a reduced interdigitation zone, subretinal drusenoid deposits, and a thinned outer nuclear layer. Electroretinogram findings ranged from abnormal oscillatory potentials to non-recordable rod responses. CONCLUSIONS: Vitamin A deficiency retinopathy can occur following medical interventions associated with malabsorption. In cases of night blindness, vitamin A levels should be measured

What would an 'ideal' glaucoma examination be like? - A conjoint analysis of patients' and physicians' preferences

PURPOSE To structurally determine patients' and physicians' preferences for glaucoma diagnostic methods in order to improve glaucoma patient care and improve patient compliance with follow-up visits. METHODS Forty-one patients with glaucoma and 32 ophthalmologists were included in this cross-sectional study. Profiles representing glaucoma examinations were created using conjoint analysis (CA). The following factors of a glaucoma examination method were evaluated: (1) examination comfort, (2) examination frequency, (3) follow-up examination necessary in case of suspicious result, (4) cost for the patient, (5) travel time to examination site, (6) sensitivity and (7) specificity of the examination method. RESULTS Preferences were highest in both groups for examination sensitivity, followed by cost and specificity for the patient group. For the physician group, specificity was second most important, followed by cost. Least important was travel time for the patients and follow-up examinations for the physicians. CONCLUSIONS Participants would rather pay more and travel longer to get a highly sensitive examination. This form of care is present in university eye hospitals. Consequently, it would be advisable to enhance capacities of these centers. Outpatient practices that offer glaucoma service should be fully equipped and should employ a glaucoma specialist

Early Visual Cultures and Panofsky’s Perspektive als ‘symbolische Form’

This paper investigates the historical dimension of perspectival representations. It aims to provide a heterogeneous though comparative picture of culturally unrelated visual con- ceptualizations of pictorial spaces, written with a view toward explaining how the multiple modes of perspective were introduced in antiquity. Point of departure for this critical approach is Erwin Panofsky’s essay Die Perspektive als ‘symbolische Form’ , published in 1927. His essay analyses the pictorial visualization of space and spatiality in different historical contexts, examining their cultural codification in terms of the heuristic category of ‘sym- bolic form’. However, ‘perspective’, which is commonly understood as synonymous with ‘linear perspective’, deserves a new discussion in the context of diverse visual cultures: A ‘naturalisation’ of the gaze as it is suggested by pictorial spaces which function mimetically is primarily associated with the early modern period in Western art. Instead of merely re- reading Panofsky’s canonical text, this paper presents an interdisciplinary re-viewing of a selection of the pictorial examples chosen by Panofsky, commenting upon their perspec- tive(s) from different vantage points

Age‐dependent retinal neuroaxonal degeneration in children and adolescents with Leber hereditary optic neuropathy under idebenone therapy

Background The aim of this study was to investigate the neuroretinal structure of young patients with Leber hereditary optic neuropathy (LHON). Methods For this retrospective cross-sectional analysis, the peripapillary retinal nerve fiber layer (pRNFL) thickness and the macular retinal layer volumes were measured by optical coherence tomography. Patients aged 12 years or younger at disease onset were assigned to the childhood-onset (ChO) group and those aged 13–16 years to the early teenage-onset (eTO) group. All patients received treatment with idebenone. The same measurements were repeated in age-matched control groups with healthy subjects. Results The ChO group included 11 patients (21 eyes) and the eTO group 14 patients (27 eyes). Mean age at onset was 8.6 ± 2.7 years in the ChO group and 14.8 ± 1.0 years in the eTO group. Mean best-corrected visual acuity was 0.65 ± 0.52 logMAR in the ChO group and 1.60 ± 0. 51 logMAR in the eTO group (p < 0.001). Reduced pRNFL was evident in the eTO group compared to the ChO group (46.0 ± 12.7 μm vs. 56.0 ± 14.5 μm, p = 0.015). Additionally, a significantly lower combined ganglion cell and inner plexiform layer volume was found in the eTO compared to the ChO group (0.266 ± 0.0027 mm3 vs. 0.294 ± 0.033 mm3, p = 0.003). No difference in these parameters was evident between the age-matched control groups. Conclusion Less neuroaxonal tissue degeneration was observed in ChO LHON than in eTO LHON, a finding that may explain the better functional outcome of ChO LHON

Severe Complications after Corneal Collagen Cross-Linking (CXL)

Purpose To present a case series of rare and severe complications after corneal collagen cross-linking (CXL) of keratoconus patients. Methods Single-center descriptive case series covering the period of 2012 to 2022 at the Department of Ophthalmology at the University Hospital, Zurich, Switzerland. Results We present four eyes of four patients that showed severe unusual complications within the first month after CXL. Three patients had been treated with the classical epithelium-off “Dresden” protocol. One patient had been treated with the accelerated epithelium-off protocol. One patient presented with extensive corneal edema due to rubbing the eye after treatment. Two patients showed a bacterial infectious keratitis: one due to Streptococcus pneumoniae and the other due to Staphylococcus hominis, Micrococcus luteus, and Streptococcus epidermidis. The latter of the two patients exhibited extensive infectious crystalline keratopathy. The fourth patient showed a severe ulcerative lesion where no infectious cause could be found. Therefore, an autoimmune keratolytic process had to be suspected. Apart from the corneal edema, which resolved ad integrum, the other complications resulted in permanent corneal scarring and thinning. One patient needed an emergency amniotic transplant. Conclusion Severe complications after CXL remain rare. Most common causes are complications that are not directly associated with the treatment as such. Those indirect complications occur after the treatment during the healing course of the epithelium. Associations with bandage contact lenses, topical steroids, atopic disease, and inappropriate patient behavior are often suspected. Correctly performed corneal scrapings with repeated microbiological analysis and a detailed patient history are essential for establishing the correct diagnosis, especially in complicated cases that do not respond to a standard therapeutic regimen. This case series supports the efforts that are currently taken to improve the CXL technique in a way that postoperative complications are further reduced. A more efficient epithelium-on technique might be a step in that direction. // Ziel Darstellung einer Fallserie von seltenen, schwerwiegenden Komplikationen nach kornealem Kollagen-Crosslinking (CXL) von Patienten mit Keratokonus. Methoden Monozentrische, beschreibende Fallserie über einen Zeitraum von 2012 bis 2022 an der Augenklinik des Universitätsspitals Zürich, Schweiz. Ergebnisse Wir zeigen 4 Augen von 4 Patienten, die mit ungewöhnlichen, schwerwiegenden Komplikationen innerhalb des 1. Monats nach CXL an unserer Klinik vorstellten. Drei der Patienten waren mit dem klassischen Epithelium-off-„Dresden“-Protokoll behandelt worden, ein Patient mit einem beschleunigten Epithelium-off-Protokoll. Ein Patient stellte sich mit einem ausgeprägten Hornhautstromaödem aufgrund von Reiben des Auges vor. Zwei Patienten zeigten eine infektiöse, bakterielle Keratitis mit Streptococcus pneumoniae bzw. Staphylococcus hominis, Micrococcus luteus, Streptococcus epidermidis. Der 4. Patient zeigte eine schwere ulzerative Läsion ohne nachweisbare infektiöse Genese, weshalb ein autoimmuner, keratolytischer Prozess vermutet wurde. Außer dem Hornhautödem, das sich vollständig zurückbildete, resultierten die anderen Komplikationen in einer bleibenden Vernarbung und Ausdünnung der Hornhaut. Ein Patient benötigte eine notfallmäßige Amnionmembrantransplantation. Schlussfolgerung Schwerwiegende Komplikationen nach CXL bleiben selten. Die häufigsten Ursachen hierfür sind Komplikationen, die nicht direkt mit der eigentlichen Prozedur zusammenhängen, sondern erst im postoperativen Heilungsverlauf des Hornhautepithels auftreten. Ein Zusammenhang mit therapeutischen Kontaktlinsen und unangemessenem Patientenverhalten wird in vielen Fällen angenommen. Korrekt durchgeführte Hornhaut-Scrapings mit wiederholter mikrobiologischer Aufarbeitung und eine detaillierte Patientenanamnese sind unerlässlich für eine korrekte Diagnosestellung, insbesondere in komplizierten Fällen, die nicht auf die üblichen Therapieregime ansprechen. Diese Fallserie unterstützt die aktuellen Bemühungen, die CXL-Technik dahingehend zu verbessern, sodass postoperative Komplikationen weiter reduziert werden. Eine effizientere Epithelium-on-Technik wäre ein Schritt in diese Richtung

Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls

Purpose: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Methods: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l’Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant’s eyes. Results: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. Conclusion: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02–0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues