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The article discusses the election of a first Latin Patriarch of Constantinople, Turkey, in the person of Thomas Morosini, following the conquest of the city by troops of the Fourth Crusade. Correspondence between Pope Innocent III and the Crusader leadership is reviewed that dealt with the assignment of official positions following the conquest and in particular the election of a Patriarch of Constantinople in the wake of the flight of the Greek Patriarch Johannes Kanateros in 2004. Details of the epistolary politics are presented.

Mutations within the COL7A1 gene underlie the inherited recessive subtype of the blistering skin disease dystrophic epidermolysis bullosa (RDEB). Although gene replacement approaches for genodermatoses are clinically advanced, their implementation for RDEB is challenging and requires endogenous regulation of transgene expression. Thus, we are using spliceosome-mediated RNA trans-splicing (SMaRT) to repair mutations in COL7A1 at the mRNA level. Here, we demonstrate the capability of a COL7A1-specific RNA trans-splicing molecule (RTM), initially selected using a fluorescence-based screening procedure, to accurately replace COL7A1 exons 1 to 64 in an endogenous setting. Retroviral RTM transduction into patient-derived, immortalized keratinocytes resulted in an increase in wild-type transcript and protein levels, respectively. Furthermore, we revealed accurate deposition of recovered type VII collagen protein within the basement membrane zone of expanded skin equivalents using immunofluorescence staining. In summary, we showed for the first time the potential of endogenous 5′ trans-splicing to correct pathogenic mutations within the COL7A1 gene. Therefore, we consider 5′ RNA trans-splicing a suitable tool to beneficially modulate the RDEB-phenotype, thus targeting an urgent need of this patient population. [ABSTRACT FROM AUTHOR]

We have studied photodetachment of the amidogen anion NH-2 as a function of photon energy near the detachment threshold. The detachment spectrum is obtained over the energy range of 6190-6355 cm-1 from the loss rate of the anions from a cryogenic radiofrequency multipole ion trap. By modeling all accessible rotational state-to-state photodetachment transitions, we can assign rotational state-specific thresholds to the measured spectrum. In thisway, we have determined the electron affinity of NH2 to be 6224 ± 1 cm-1. © 2018 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license. [ABSTRACT FROM AUTHOR]

The Duchenne muscular dystrophy (DMD) gene has a complex expression pattern regulated by multiple tissue-specific promoters and by alternative splicing (AS) of the resulting transcripts. Here, we used an RNAi-based approach coupled with DMD-targeted RNA-seq to identify RNA-binding proteins (RBPs) that regulate splicing of its skeletal muscle isoform (Dp427m) in a human muscular cell line. A total of 16 RBPs comprising the major regulators of muscle-specific splicing events were tested. We show that distinct combinations of RBPs maintain the correct inclusion in the Dp427m of exons that undergo spatio-temporal AS in other dystrophin isoforms. In particular, our findings revealed the complex networks of RBPs contributing to the splicing of the two short DMD exons 71 and 78, the inclusion of exon 78 in the adult Dp427m isoform being crucial for muscle function. Among the RBPs tested, QKI and DDX5/DDX17 proteins are important determinants of DMD exon inclusion. This is the first large-scale study to determine which RBP proteins act on the physiological splicing of the DMD gene. Our data shed light on molecular mechanisms contributing to the expression of the different dystrophin isoforms, which could be influenced by a change in the function or expression level of the identified RBPs. [ABSTRACT FROM AUTHOR]

Background: Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP). Methods: Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons' directors or medical directors between November 2021-May 2022. Results: According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy. Conclusions: To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities. [ABSTRACT FROM AUTHOR]

Mutations in the COL7A1 gene lead to malfunction, reduction or complete absence of type VII collagen (C7) in the skin's basement membrane zone (BMZ), impairing skin integrity. In epidermolysis bullosa (EB), more than 800 mutations in COL7A1 have been reported, leading to the dystrophic form of EB (DEB), a severe and rare skin blistering disease associated with a high risk of developing an aggressive form of squamous cell carcinoma. Here, we leveraged a previously described 3′-RTMS6m repair molecule to develop a non-viral, non-invasive and efficient RNA therapy to correct mutations within COL7A1 via spliceosome-mediated RNA trans-splicing (SMaRT). RTM-S6m, cloned into a non-viral minicircle-GFP vector, is capable of correcting all mutations occurring between exon 65 and exon 118 of COL7A1 via SMaRT. Transfection of the RTM into recessive dystrophic EB (RDEB) keratinocytes resulted in a trans-splicing efficiency of ~1.5% in keratinocytes and ~0.6% in fibroblasts, as confirmed on mRNA level via next-generation sequencing (NGS). Full-length C7 protein expression was primarily confirmed in vitro via immunofluorescence (IF) staining and Western blot analysis of transfected cells. Additionally, we complexed 3′-RTMS6m with a DDC642 liposomal carrier to deliver the RTM topically onto RDEB skin equivalents and were subsequently able to detect an accumulation of restored C7 within the basement membrane zone (BMZ). In summary, we transiently corrected COL7A1 mutations in vitro in RDEB keratinocytes and skin equivalents derived from RDEB keratinocytes and fibroblasts using a non-viral 3′-RTMS6m repair molecule. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate real world efficacy and safety of the Preserflo MicroShunt (PM) in a heterogenous patient cohort at a single tertiary eye care centre.A retrospective data analysis of PM implantations between 2019 and 2022 was performed. Primary outcome measures were complete-, qualified-, and overall- success as well as failure defined according to the WGA criteria. Secondary outcomes were intraocular pressure (IOP) and IOP lowering medications.38 patients were included in the study. After 24 months, complete success was achieved in 31.58% and qualified success in 28.95% whereas 39.47% were classified as failure. IOP was reduced by 55.2% from mean 25.57 ± 10.03 mmHg at baseline to 11.45 ± 3.37 mmHg two years postoperative in eyes classified as success. The number of IOP lowering medications was reduced from 2.73 ± 1.33 before surgery to 1.14 ± 1.31 at the end of the follow-up period.Two years postoperatively an overall success rate of 60.53% was achieved and a significant IOP reduction was preserved over the complete two years follow-up time.What is knownMultiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. Multiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. What is newReal world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Real world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Patients and methods: To evaluate real world efficacy and safety of the Preserflo MicroShunt (PM) in a heterogenous patient cohort at a single tertiary eye care centre.A retrospective data analysis of PM implantations between 2019 and 2022 was performed. Primary outcome measures were complete-, qualified-, and overall- success as well as failure defined according to the WGA criteria. Secondary outcomes were intraocular pressure (IOP) and IOP lowering medications.38 patients were included in the study. After 24 months, complete success was achieved in 31.58% and qualified success in 28.95% whereas 39.47% were classified as failure. IOP was reduced by 55.2% from mean 25.57 ± 10.03 mmHg at baseline to 11.45 ± 3.37 mmHg two years postoperative in eyes classified as success. The number of IOP lowering medications was reduced from 2.73 ± 1.33 before surgery to 1.14 ± 1.31 at the end of the follow-up period.Two years postoperatively an overall success rate of 60.53% was achieved and a significant IOP reduction was preserved over the complete two years follow-up time.What is knownMultiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. Multiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. What is newReal world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Real world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Result: To evaluate real world efficacy and safety of the Preserflo MicroShunt (PM) in a heterogenous patient cohort at a single tertiary eye care centre.A retrospective data analysis of PM implantations between 2019 and 2022 was performed. Primary outcome measures were complete-, qualified-, and overall- success as well as failure defined according to the WGA criteria. Secondary outcomes were intraocular pressure (IOP) and IOP lowering medications.38 patients were included in the study. After 24 months, complete success was achieved in 31.58% and qualified success in 28.95% whereas 39.47% were classified as failure. IOP was reduced by 55.2% from mean 25.57 ± 10.03 mmHg at baseline to 11.45 ± 3.37 mmHg two years postoperative in eyes classified as success. The number of IOP lowering medications was reduced from 2.73 ± 1.33 before surgery to 1.14 ± 1.31 at the end of the follow-up period.Two years postoperatively an overall success rate of 60.53% was achieved and a significant IOP reduction was preserved over the complete two years follow-up time.What is knownMultiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. Multiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. What is newReal world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Real world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Conclusion: To evaluate real world efficacy and safety of the Preserflo MicroShunt (PM) in a heterogenous patient cohort at a single tertiary eye care centre.A retrospective data analysis of PM implantations between 2019 and 2022 was performed. Primary outcome measures were complete-, qualified-, and overall- success as well as failure defined according to the WGA criteria. Secondary outcomes were intraocular pressure (IOP) and IOP lowering medications.38 patients were included in the study. After 24 months, complete success was achieved in 31.58% and qualified success in 28.95% whereas 39.47% were classified as failure. IOP was reduced by 55.2% from mean 25.57 ± 10.03 mmHg at baseline to 11.45 ± 3.37 mmHg two years postoperative in eyes classified as success. The number of IOP lowering medications was reduced from 2.73 ± 1.33 before surgery to 1.14 ± 1.31 at the end of the follow-up period.Two years postoperatively an overall success rate of 60.53% was achieved and a significant IOP reduction was preserved over the complete two years follow-up time.What is knownMultiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. Multiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. What is newReal world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Real world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Key Messages: To evaluate real world efficacy and safety of the Preserflo MicroShunt (PM) in a heterogenous patient cohort at a single tertiary eye care centre.A retrospective data analysis of PM implantations between 2019 and 2022 was performed. Primary outcome measures were complete-, qualified-, and overall- success as well as failure defined according to the WGA criteria. Secondary outcomes were intraocular pressure (IOP) and IOP lowering medications.38 patients were included in the study. After 24 months, complete success was achieved in 31.58% and qualified success in 28.95% whereas 39.47% were classified as failure. IOP was reduced by 55.2% from mean 25.57 ± 10.03 mmHg at baseline to 11.45 ± 3.37 mmHg two years postoperative in eyes classified as success. The number of IOP lowering medications was reduced from 2.73 ± 1.33 before surgery to 1.14 ± 1.31 at the end of the follow-up period.Two years postoperatively an overall success rate of 60.53% was achieved and a significant IOP reduction was preserved over the complete two years follow-up time.What is knownMultiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. Multiple studies have proven that the Preserflo MicroShunt is a safe and efficient surgical procedure to lower intraocular pressure.The success rates reported for primary open angle glaucoma are comparable to trabeculectomy. What is newReal world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period.Real world data including different glaucoma subtypes at one tertiary care centre are reported with a two-year follow up.An overall surgical success rate of 60.53% was achieved.An intraocular pressure reduction of 50.2% was sustained over the two years follow up period. [ABSTRACT FROM AUTHOR]

Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases. [ABSTRACT FROM AUTHOR]

Background: Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods: MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results: Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion: The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA. [ABSTRACT FROM AUTHOR]

As one of the most frequently occurring monomers in the biosphere, glucosamine is a valuable metabolite for several applications. Although microbial glucosamine production is still in its infancy, it offers the possibility to circumvent problems associated with traditional production by hydrolysis. Of particular interest is a study with Aspergillus niger, which reports for the first time high glucosamine excretion in the early phase of citric acid production. These results have relevance for both the commercial glucosamine production and deeper insight into the regulation of organic acid excretion in fungi. To investigate glucosamine excretion, we performed bioreactor batch cultivations with Penicillium ochrochloron CBS123.824 and A. niger CBS120.49 using cultivation conditions which are known to trigger the production of citric acid. Glucosamine detection in culture filtrates was achieved by two photometric methods, High performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) and HPLC with mass spectrometry detection (HPLC-MS). Surprisingly, we detected no glucosamine at all. Based on a critical review of published data for A. niger, we conclude that the reported high levels of excreted glucosamine might be an experimental artifact. However, growth experiments with glucosamine as a combined or single source for carbon or nitrogen showed that both organisms are in principle able to transport glucosamine across their plasma membrane, which is a prerequisite for the excretion of glucosamine.