Comparison of Wash-out Properties after Use of the Vital Dye Trypan Blue in the Form of an Ophthalmic Dye and Bound in a Sodium Hyaluronate by Raman Spectroscopy

In cataract surgery, the creation of the anterior capsulorhexis as one of the critical steps is of most importance for the surgical success. In challenging initial situations (e.g. in eyes with pseudoexfoliation syndrome, mature, brunescent cataract, juvenile cataract, corneal opacities, or in post-traumatic and postuveitic cases), vital dyes are used as a routine to increase the visibility and plasticity of the ocular structures in the anterior chamber. The range of applications of the vital dye trypan blue (TB) has expanded considerably in recent years due to its excellent staining properties.1 However, its use in ophthalmology as an effective and useful tool requires that the dye has no adverse effects on the cell structures of the eye. As two laboratory studies on cell cultures showed, the time of exposure to TB plays an important role in addition to concentration.2,3 The in vitro studies by Chang et al. with rabbit corneal endothelial cell cultures, and van Dooren et al.3 demonstrated no toxicity of TB with a maximum concentration of 0.4% after 1 minute in cell cultures of human corneal fibroplasts. A significant toxicity of a TB concentration of 0.01% or higher after exposure was observed. At 24-hour exposure, a TB concentration of 0.005% was found to be the threshold for a significant cytotoxicity index. In principle, it is important to note that trypan blue can be cytotoxic at a certain concentration. Monoazo, the most toxic of known impurities found in trypan blue dyes can be carcinogenic. However, the TB concentrations used in eye surgery do not have undesirable effects on the cell structures of the eye and are therefore generally considered safe.3,4 However, a case report showed a transient retinal toxic reaction in the form of transient visual field defect following the entry of TB into the vitreous body space.5 In modern intraocular procedures viscoelastic substances (OVDs, ophthalmic viscoelastic devices) are widely used. Since their introduction in the 1970s, they have been routinely used in cataract surgery and serve to protect sensitive eye structures from mechanical injuries or to create and maintain anatomical spaces such as the anterior chamber or the capsular bag. They increase safety during the procedure and can also shorten overall surgery time by improving visibility and simplifying some surgical steps for the surgeon.6 A shorter surgery time is associated with a lower degree of trauma and a lower risk of complications, and may ultimately be associated with faster recovery and a better final outcome and satisfaction for the patient. In addition, from an economic point of view, the time saving factor is particularly important for high-volume facilities. After the introduction of Healon® in 1979, sodium hyaluronate became the most widely used biopolymer for OVDs in intraocular surgery. Since then, the pharmacological, physiological, and clinical aspects of sodium hyaluronate for ophthalmic applications have been assessed in a large number of studies.7,8 Recently, a combination of a viscoelastic with the vital dye TB has been introduced (Pe-Ha-Blue®PLUS, Albomed, Schwarzenbruck, Germany) and has already been clinically investigated in a prospective case series of 52 eyes with pseudoexfoliation syndrome.6 In addition to a significantly shorter surgery time (due to fewer individual surgical steps) with cost- and safety-relevant advantages of Pe-Ha-Blue®PLUS compared to separate administration of OVD (POLY-HYL® 1. 6%; Polytech Domilens GmbH) and TB (Vision Blue®; DORC, Holland/Blue Color Caps®), the surgeon gains better control over whether the OVD is removed completely at the end of surgery by using the blue OVD. This should also reduce postoperative complications such as hypertension due to OVD residues remaining in the eye. The aim of the present in vitro study was to determine by Raman spectroscopy the amount of residue of the TB dye that remains on a slide during the routine application of two commercial products (TB dye Vision Blue® and Pe-Ha-Blue®PLUS). In Raman spectroscopy, the interaction of light and matter is used to investigate, for example, the properties of a material or to enable the microscopic examination of materials. Excited by monochromatic light, the sample emits scattered light with a specific frequency shift. The frequency shift (the so-called Raman shift) contain information about the vibrational states of the molecules and thus about the chemical composition and structure of the sample. This phenomenon was discovered by Sir C. V. Raman in the early 20th century. Since the beginning of the 20th century, the method, today mostly stimulated by a laser light source, is widely used in fields such as industry, chemistry, archaeology or for the qualitative and quantitative analysis of products in the pharmaceutical industry

Efficacy of Off-Label Anti-Amoebic Agents to Suppress Trophozoite Formation of Acanthamoeba spp. on Non-Nutrient Agar Escherichia Coli Plates

Acanthamoeba keratitis (AK) is a dangerous infectious disease, which is associated with a high risk of blindness for the infected patient, and for which no standard therapy exists thus far. Patients suffering from AK are thus treated, out of necessity, with an off-label therapy, using drugs designed and indicated for other diseases/purposes. Here, we tested the capability of the off-label anti-amoebic drugs chlorhexidine (CH; 0.1%), dibromopropamidine diisethionate (DD; 0.1%), hexamidine diisethionate (HD; 0.1%), miltefosine (MF; 0.0065%), natamycin (NM; 5%), polyhexamethylene biguanide (PHMB; 0.02%), povidone iodine (PVPI; 1%), and propamidine isethionate (PD; 0.1%) to suppress trophozoite formation of Acantamoeba castellanii and Acanthamoeba hatchetti cysts on non-nutrient agar Escherichia coli plates. Of the eight off-label anti-amoebic drugs tested, only PVPI allowed for a complete suppression of trophozoite formation by drug-challenged cysts for all four Acanthamoeba isolates in all five biological replicates. Drugs such as NM, PD, and PHMB repeatedly suppressed trophozoite formation with some, but not all, tested Acanthamoeba isolates, while other drugs such as CH, DD, and MF failed to exert a relevant effect on the excystation capacities of the tested Acanthamoeba isolates in most, if not all, of our repetitions. Our findings suggest that pre-testing of the AK isolate with the non-nutrient agar E. coli plate assay against the anti-amoebic drug intended for treatment should be performed to confirm that the selected drug is cysticidal for the Acanthamoeba isolate

APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0–5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation

Managerial power in the German model: the case of Bertelsmann and the antecedents of neoliberalism

Our article extends the research on authoritarian neoliberalism to Germany, through a history of the Bertelsmann media corporation – sponsor and namesake of Germany’s most influential neoliberal think-tank. Our article makes three conceptual moves. Firstly, we argue that conceptualizing German neoliberalism in terms of an ‘ordoliberal paradigm’ is of limited use in explaining the rise and fall of Germany’s distinctive socio-economic model (Modell Deutschland). Instead, we locate the origins of authoritarian tendencies in the corporate power exercised by managers rather than in the power of state-backed markets imagined by ordoliberals. Secondly, we focus on the managerial innovations of Bertelsmann as a key actor enmeshed with Modell Deutschland. We show that the adaptation of business management practices of an endogenous ‘Cologne School’ empowered Bertelsmann’s postwar managers to overcome existential crises and financial constraints despite being excluded from Germany’s corporate support network. Thirdly, we argue that their further development in the 1970s also enabled Bertelsmann to curtail and circumvent the forms of labour representation associated with Modell Deutschland. Inspired by cybernetic management theories that it used to limit and control rather than revive market competition among its workforce, Bertelsmann began to act and think outside the postwar settlement between capital and labour before the settlement’s hotly-debated demise since the 1990s